Pulmonary Disease, Chronic Obstructive, Pulmonary Emphysema
Conditions
Brief summary
The study will include 60 healthy subjects (ex-smoker without any airflow limitation), 125 COPD GOLD (global initiative for chronic obstructive lung disease) I , 125 COPD GOLD II, 125 COPD GOLD III and up to 20 patients with COPD and A1AT (Alpha1-Antitrypsin) deficiency (ZZ genotype). Soluble and imaging biomarkers will be investigated addressing different aspects of disease pathways postulated to be relevant for COPD progression.
Interventions
None listed
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
40 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
General Inclusion Criteria * Male or female healthy subjects or COPD (GOLD I to III) outpatients with or without A1AT deficiency * Ex-smokers for at least 9 months with a smoking history of \>=20 pack years * Signed informed consent consistent with ICH-GCP (International Conference on Harmonisation - Good Clinical Practice) guidelines prior to participation in the study, which includes the application of study restrictions * Age \>= 40 and \<=70 years * Body mass index (BMI) of \>= 18 and \<= 35 kg/m2 (\<= 30 kg/m2 in the MRI subset) * Ability to perform all study related procedures including technically acceptable pulmonary function tests, body plethysmography, DLCO ( Diffusing Capacity of the lungs for Carbon Monoxide) , sputum induction (if applicable), chest CT (Computed Tomography) and MRI (if applicable) Inclusion Criteria Specific for Patients with COPD - Patients must have a current diagnosis of COPD made by a physician prior to or during Visit 1 and a mMRC (Modified Medical Research Council Dyspnea Scale) score of 1 or more. The diagnosis of COPD must be in accordance with GOLD Guidelines and must be documented by the following criteria: Known relatively stable airway obstruction with a post-bronchodilator FEV1 (Forced Expiratory Volume in first second)/FVC (Forced Vital Capacity) \< 70 % * The current COPD must be mild, moderate or severe based on lung functions and symptoms and the clinical situation must have stabilized for at least 4 weeks prior to Visit 1. The following definitions adapted from the GOLD Guidelines apply: 1. mild: post-broncho-dilator FEV1 \>=80% of predicted normal (GLI 2012 and JRS 2014) at Visit 1 2. moderate: 50%\<= post-broncho-dilator FEV1 \< 80% of predicted normal (GLI 2012 and JRS 2014) without chronic respiratory failure at Visit 1 3. severe: 30%\<= post-bronchodilator FEV1 \<50% of predicted normal (GLI 2012 and JRS 2014) without chronic respiratory failure at Visit 1 * Patients must be on stable therapy (not limited to respiratory medication) for the last 4 weeks prior to Visit 1 Inclusion Criteria Specific Patients with COPD and A1AT Deficiency \- Documented A1AT deficiency of ZZ genotype Inclusion Criteria Specific Healthy Subjects * Normal lung function values at Visit 1 with a documented post-bronchodilator FEV1 \>=80% of predicted normal (GLI 2012 and JRS 2014) and a post-bronchodilator FEV1/FVC \>= lower limit of normal * Mean post DLCO over all acceptable measurements at Visit 1 of \>= 70% of predicted normal * Further inclusion criteria apply
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume | Up to Week 156. Change from baseline value at Week 156 was reported. | The absolute change from baseline at Week 156 in adjusted lung density (ALD) based on Percentile Density at 15% (PD15) adjusted for lung volume was reported. The ALD was calculated as: Percentile Density at 15% (PD15) \[gram/Liter (L)\] \* (Inspiratory volume \[L\]/predicted total lung volume \[L\]). The absolute change from baseline in ALD gram/Liter (g/L) was analyzed by Mixed Model for Repeated Measures (MMRM). |
| Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1) | Up to Week 156 | The annual rate of lung function decline based on Forced Expiratory Volume in 1 second (FEV1) was reported. The annual rate was estimated from a random slope and intercept model with fixed categorical effects of diagnosis group, fixed continuous effects of time \[Year\], and including diagnosis group-by-time interaction. Random effect was included for subject specific intercept and time. Within-subject errors are modelled by an unstructured variance-covariance matrix. |
| Number of Participants by the Category of Number of Exacerbations During Study | Up to Week 156 | Number of participants by the category of number of exacerbations (no exacerbation, 1 exacerbation, or \>= 2 exacerbations) during study was reported. |
| Duration of Exacerbations During Study (Per Year) | Up to 156 weeks | The duration of exacerbations for each subject was calculated as: sum of duration of episodes during study (days)\*(365.25/ number of days in study). |
| Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | Up to 156 weeks | Number of participants with at least moderate exacerbation during study by the category of number of moderate exacerbation (no moderate exacerbation, 1 moderate exacerbation, or \>= 2 moderate exacerbations) was reported. |
| Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | Up to 156 weeks | Number of participants with severe exacerbations during study by the category of number of severe exacerbations (no severe exacerbation, 1 severe exacerbation, or \>= 2 severe exacerbations) was reported. |
Countries
Belgium, Canada, Denmark, Finland, Germany, Japan, Poland, South Korea, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
The overall objective of this study is to explore, if any of the biomarkers (soluble, functional imaging and physiological) assessed within healthy subjects, patients with Chronic Obstructive Pulmonary Disease (COPD) and patients with COPD and Alpha-1 Antitrypsin (A1AT) deficiency are correlated to COPD disease progression, particularly emphysema progression over 156 weeks.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Subjects All eligible healthy subjects were included in this group. The observational period is 156 weeks. | 62 |
| COPD GOLD I All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 1 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks. | 123 |
| COPD GOLD II All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 2 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks. | 130 |
| COPD GOLD III All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) grade 3 according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) were included in this group. The observational period is 156 weeks. | 129 |
| COPD and A1AT Deficiency All eligible patients with Chronic Obstructive Pulmonary Disease (COPD) and Alpha one anti-trypsin (A1AT) deficiency were included in this group. The observational period is 156 weeks. | 19 |
| Total | 463 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 3 | 0 |
| Overall Study | Lost to Follow-up | 0 | 4 | 1 | 3 | 0 |
| Overall Study | Other than listed | 1 | 12 | 13 | 22 | 9 |
| Overall Study | Protocol Violation | 0 | 3 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 3 | 6 | 6 | 0 |
Baseline characteristics
| Characteristic | Healthy Subjects | Total | COPD and A1AT Deficiency | COPD GOLD III | COPD GOLD II | COPD GOLD I |
|---|---|---|---|---|---|---|
| Adjusted lung density (ALD) | 88.50 gram/Liter STANDARD_DEVIATION 13.9 | 73.62 gram/Liter STANDARD_DEVIATION 24.92 | 50.86 gram/Liter STANDARD_DEVIATION 18.15 | 54.81 gram/Liter STANDARD_DEVIATION 23.08 | 72.42 gram/Liter STANDARD_DEVIATION 21.69 | 86.20 gram/Liter STANDARD_DEVIATION 21.38 |
| Age, Continuous | 54.0 Years STANDARD_DEVIATION 6.8 | 60.7 Years STANDARD_DEVIATION 6.8 | 52.8 Years STANDARD_DEVIATION 9 | 62.9 Years STANDARD_DEVIATION 5.6 | 61.8 Years STANDARD_DEVIATION 5.3 | 61.9 Years STANDARD_DEVIATION 6.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 7 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 61 Participants | 451 Participants | 18 Participants | 124 Participants | 127 Participants | 121 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 5 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 37 Participants | 0 Participants | 6 Participants | 7 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 10 Participants | 0 Participants | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 00 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 52 Participants | 413 Participants | 19 Participants | 119 Participants | 117 Participants | 106 Participants |
| Sex: Female, Male Female | 23 Participants | 164 Participants | 3 Participants | 49 Participants | 52 Participants | 37 Participants |
| Sex: Female, Male Male | 39 Participants | 299 Participants | 16 Participants | 80 Participants | 78 Participants | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 123 | 0 / 130 | 0 / 129 | 0 / 19 |
| other Total, other adverse events | 0 / 62 | 0 / 123 | 0 / 130 | 0 / 129 | 0 / 19 |
| serious Total, serious adverse events | 0 / 62 | 0 / 123 | 0 / 130 | 0 / 129 | 0 / 19 |
Outcome results
Primary
Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume
The absolute change from baseline at Week 156 in adjusted lung density (ALD) based on Percentile Density at 15% (PD15) adjusted for lung volume was reported. The ALD was calculated as: Percentile Density at 15% (PD15) \[gram/Liter (L)\] \* (Inspiratory volume \[L\]/predicted total lung volume \[L\]). The absolute change from baseline in ALD gram/Liter (g/L) was analyzed by Mixed Model for Repeated Measures (MMRM).
Time frame: Up to Week 156. Change from baseline value at Week 156 was reported.
Population: Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments. Only participants with non-missing results were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects | Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume | -0.27 gram/Liter (g/L) | Standard Error 1 |
| COPD GOLD I | Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume | -3.15 gram/Liter (g/L) | Standard Error 0.79 |
| COPD GOLD II | Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume | -5.04 gram/Liter (g/L) | Standard Error 0.84 |
| COPD GOLD III | Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume | -4.74 gram/Liter (g/L) | Standard Error 1.04 |
| COPD and A1AT Deficiency | Absolute Change From Baseline at Week 156 in Adjusted Lung Density (ALD) Based on Percentile Density at 15% (PD15) Adjusted for Lung Volume | -6.13 gram/Liter (g/L) | Standard Error 2.51 |
p-value: 0.020295% CI: [-5.32, -0.45]Mixed Model for Repeated Measures (MMRM)
p-value: 0.000395% CI: [-7.36, -2.19]Mixed Model for Repeated Measures (MMRM)
p-value: 0.003395% CI: [-7.44, -1.5]Mixed Model for Repeated Measures (MMRM)
p-value: 0.033495% CI: [-11.26, -0.47]Mixed Model for Repeated Measures (MMRM)
Primary
Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1)
The annual rate of lung function decline based on Forced Expiratory Volume in 1 second (FEV1) was reported. The annual rate was estimated from a random slope and intercept model with fixed categorical effects of diagnosis group, fixed continuous effects of time \[Year\], and including diagnosis group-by-time interaction. Random effect was included for subject specific intercept and time. Within-subject errors are modelled by an unstructured variance-covariance matrix.
Time frame: Up to Week 156
Population: Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments. Only participants with non-missing results were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects | Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1) | -25.7 milliliter / year [mL/year] | Standard Error 11.4 |
| COPD GOLD I | Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1) | -24.4 milliliter / year [mL/year] | Standard Error 8.9 |
| COPD GOLD II | Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1) | -44.9 milliliter / year [mL/year] | Standard Error 9.6 |
| COPD GOLD III | Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1) | -59.3 milliliter / year [mL/year] | Standard Error 11.4 |
| COPD and A1AT Deficiency | Annual Rate of Lung Function Decline Based on Forced Expiratory Volume in 1 Second (FEV1) | -87.5 milliliter / year [mL/year] | Standard Error 28 |
p-value: 0.930695% CI: [-27.2, 29.7]Random slope and intercept model
p-value: 0.198395% CI: [-48.5, 10.1]Random slope and intercept model
p-value: 0.038195% CI: [-65.4, -1.9]Random slope and intercept model
p-value: 0.041995% CI: [-121.3, -2.3]Random slope and intercept model
Primary
Duration of Exacerbations During Study (Per Year)
The duration of exacerbations for each subject was calculated as: sum of duration of episodes during study (days)\*(365.25/ number of days in study).
Time frame: Up to 156 weeks
Population: Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments. Only participants with non-missing results were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Subjects | Duration of Exacerbations During Study (Per Year) | 13.1 days/year | Standard Deviation 5.2 |
| COPD GOLD I | Duration of Exacerbations During Study (Per Year) | 9.7 days/year | Standard Deviation 13 |
| COPD GOLD II | Duration of Exacerbations During Study (Per Year) | 18.0 days/year | Standard Deviation 19.4 |
| COPD GOLD III | Duration of Exacerbations During Study (Per Year) | 19.7 days/year | Standard Deviation 24.2 |
| COPD and A1AT Deficiency | Duration of Exacerbations During Study (Per Year) | 17.8 days/year | Standard Deviation 16.7 |
Primary
Number of Participants by the Category of Number of Exacerbations During Study
Number of participants by the category of number of exacerbations (no exacerbation, 1 exacerbation, or \>= 2 exacerbations) during study was reported.
Time frame: Up to Week 156
Population: Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments. Only participants with non-missing results were included in the analysis
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy Subjects | Number of Participants by the Category of Number of Exacerbations During Study | 0 | 59 Participants |
| Healthy Subjects | Number of Participants by the Category of Number of Exacerbations During Study | >= 2 | 1 Participants |
| Healthy Subjects | Number of Participants by the Category of Number of Exacerbations During Study | 1 | 1 Participants |
| COPD GOLD I | Number of Participants by the Category of Number of Exacerbations During Study | 1 | 23 Participants |
| COPD GOLD I | Number of Participants by the Category of Number of Exacerbations During Study | 0 | 89 Participants |
| COPD GOLD I | Number of Participants by the Category of Number of Exacerbations During Study | >= 2 | 10 Participants |
| COPD GOLD II | Number of Participants by the Category of Number of Exacerbations During Study | 1 | 24 Participants |
| COPD GOLD II | Number of Participants by the Category of Number of Exacerbations During Study | 0 | 66 Participants |
| COPD GOLD II | Number of Participants by the Category of Number of Exacerbations During Study | >= 2 | 37 Participants |
| COPD GOLD III | Number of Participants by the Category of Number of Exacerbations During Study | 0 | 41 Participants |
| COPD GOLD III | Number of Participants by the Category of Number of Exacerbations During Study | >= 2 | 56 Participants |
| COPD GOLD III | Number of Participants by the Category of Number of Exacerbations During Study | 1 | 30 Participants |
| COPD and A1AT Deficiency | Number of Participants by the Category of Number of Exacerbations During Study | 1 | 4 Participants |
| COPD and A1AT Deficiency | Number of Participants by the Category of Number of Exacerbations During Study | 0 | 2 Participants |
| COPD and A1AT Deficiency | Number of Participants by the Category of Number of Exacerbations During Study | >= 2 | 13 Participants |
Primary
Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations
Number of participants with at least moderate exacerbation during study by the category of number of moderate exacerbation (no moderate exacerbation, 1 moderate exacerbation, or \>= 2 moderate exacerbations) was reported.
Time frame: Up to 156 weeks
Population: Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments. Only participants with non-missing results were included in the analysis
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy Subjects | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 0 | 60 Participants |
| Healthy Subjects | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | >= 2 | 0 Participants |
| Healthy Subjects | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 1 | 1 Participants |
| COPD GOLD I | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 1 | 20 Participants |
| COPD GOLD I | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 0 | 93 Participants |
| COPD GOLD I | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | >= 2 | 9 Participants |
| COPD GOLD II | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 1 | 22 Participants |
| COPD GOLD II | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 0 | 73 Participants |
| COPD GOLD II | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | >= 2 | 32 Participants |
| COPD GOLD III | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 0 | 48 Participants |
| COPD GOLD III | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | >= 2 | 50 Participants |
| COPD GOLD III | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 1 | 29 Participants |
| COPD and A1AT Deficiency | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 1 | 8 Participants |
| COPD and A1AT Deficiency | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | 0 | 4 Participants |
| COPD and A1AT Deficiency | Number of Participants With at Least Moderate Exacerbation During Study by the Category of Number of Moderate Exacerbations | >= 2 | 7 Participants |
Primary
Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations
Number of participants with severe exacerbations during study by the category of number of severe exacerbations (no severe exacerbation, 1 severe exacerbation, or \>= 2 severe exacerbations) was reported.
Time frame: Up to 156 weeks
Population: Per-Protocol Set (Biomarker Subjects): All subjects, from the Observed subjects set, who have no Important Protocol Deviations (IPDs) affecting the clinical or biomarker assessments. Only participants with non-missing results were included in the analysis
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy Subjects | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | >= 2 | 0 Participants |
| Healthy Subjects | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 0 | 61 Participants |
| Healthy Subjects | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 1 | 0 Participants |
| COPD GOLD I | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | >= 2 | 1 Participants |
| COPD GOLD I | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 0 | 120 Participants |
| COPD GOLD I | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 1 | 1 Participants |
| COPD GOLD II | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 1 | 9 Participants |
| COPD GOLD II | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 0 | 118 Participants |
| COPD GOLD II | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | >= 2 | 0 Participants |
| COPD GOLD III | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 1 | 19 Participants |
| COPD GOLD III | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 0 | 103 Participants |
| COPD GOLD III | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | >= 2 | 5 Participants |
| COPD and A1AT Deficiency | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | >= 2 | 2 Participants |
| COPD and A1AT Deficiency | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 0 | 16 Participants |
| COPD and A1AT Deficiency | Number of Participants With Severe Exacerbations During Study by the Category of Number of Severe Exacerbations | 1 | 1 Participants |