Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, Smokers, Ex-smokers
Brief summary
The purpose of this study was to assess global ventilated lung volume in moderate to severe COPD patients using MRI lung imaging after treatment with QVA149 compared to placebo.
Detailed description
The MRI approach represented an opportunity to better understand the impact of a potent dual bronchodilator on the small and central airways and thereby increasing ventilated lung volume, gas exchange, and ventilation-perfusion deficits. The study investigated the effect of QVA149 on global and regional lung ventilation using MRI lung imaging to enhance the understanding of QVA pharmacology in COPD patients.
Interventions
DRUGQVA149
QVA149 110/50 μg o.d. capsules for inhalation, supplied in blisters via the Concept 1 inhalation device, a single dose dry powder inhaler.
DRUGPlacebo
Matching placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Males and females with COPD aged 40 years and above, weighing ≥45 kg and ≤100 kg, who were smokers and ex-smokers who had a smoking history of at least 10 pack years, and diagnosed with moderate to severe COPD according to GOLD 2015 criteria were included in the study. Patients with airflow limitation indicated by a post-bronchodilator FEV1/FVC \< 0.70 and by a post-bronchodilator FEV1 ≥ 30 % and \<80 % were included in the study. Post-bronchodilator refers to 1 hr (+/- 5 minutes) after sequential inhalation of 84 µg ipratropium bromide (or equivalent dose) and 400 µg salbutamol/360 µg albuterol (or equivalent dose). Key
Exclusion criteria
Patients with conditions which could compromise patient safety and compliance (as judged by the investigator), as well as conditions that required oxygen therapy for chronic hypoxemia, ≥25% emphysematous changes on a scan within 6 months to screening, those with lower respiratory infections within 6 weeks of screening, and patients with concomitant pulmonary disease were excluded from the study. Patients with asthma were also excluded from the study. Pregnant or nursing (lactating) women, patients with poorly controlled Type I or Type II diabetes, patients with poor renal function, and those who were unable to use a dry powder inhaler or perform spirometry, and had contraindications to MRI were also excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global Ventilated Lung Volume | Day 8 to Day 10 (each treatment period) | The global distribution of inhaled gas within the lung was assessed using an inhaled gaseous contrast agent, Hyperpolarized Helium (3He) Lung Imaging. The Global Ventilated Lung Volume was expressed in percentage (%VV) of total lung volume. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Regional Ventilated Lung Volume | Day 8 to Day 10 (each treatment period) | The regional distribution of inhaled gas within the lung was assessed using an inhaled gaseous contrast agent, Hyperpolarized Helium (3He) Lung Imaging. The Regional Ventilated Lung Volume was expressed in percentage (% VDV) of total lung volume for each lobar region. |
| Pulmonary Perfusion | Day 8 to Day 10 (each treatment period) | Lung Perfusion Imaging, or MR perfusion imaging of the lung with gadolinium contrast agent, was performed to determine whether vascular abnormalities producing perfusion deficits corresponded to abnormalities in ventilation (hypoxic vasoconstriction). Pulmonary Perfusion was expressed in ml/100 g lung tissue/min of each lobar region. |
| Forced Expiratory Volume in 1 Second (FEV1) | Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period) | The Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. |
| Forced Vital Capacity (FVC) | Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period) | Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. An increase in FVC indicates improvement in lung function. |
| FEV1/FVC Ratio | Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period) | The FEV1/FVC ratio is the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC). The result of this ratio is expressed as FEV1%. |
| Lung Clearance Index by Multiple Breath Nitrogen Washout (MBNW) | Day 8 (each treatment period) | Multiple Breath Nitrogen Washout (MBNW) was performed after 2 hours post-dose spirometry assessments using a multiple breath inert gas washout technique. The device provides the global index of ventilation inhomogeneity assessment (LCI = Cumulative Expired Volume/Functional Residual Capacity). |
| Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | Day 8 (each treatment period) | The diffusing capacity of the lung for carbon monoxide (DLCO) is a measure of how easily carbon monoxide (CO) molecules transfer from the alveolar gas to the hemoglobin of the red cells in the pulmonary circulation. To measure the DLCO, the patient inhales a single breath containing a minute amount of CO and holds it for 10 seconds. The breath is then exhaled and the exhaled breath is analyzed for CO. The change in the concentration of the CO is then multiplied by the single breath TLC to calculate the DLCO. |
Countries
United Kingdom
Participant flow
Recruitment details
The study took place in 3 clinical sites in United-Kingdom
Pre-assignment details
31 patients were randomized, all of whom were included in the safety set and PD analysis sets (primary population of interest)
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either QVA149 110/50 mcg or Placebo matching QVA149 110/50 mcg | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 (Second Treatment, 8-10 Days) | Adverse Event | 2 | 0 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 65.9 Years STANDARD_DEVIATION 6.31 |
| FEV1/FVC ratio 0 Minutes Pre Inhalation | 42.968 Percent ((FEV1/FVC)*100) STANDARD_DEVIATION 8.9797 |
| FEV1/FVC ratio 60 Minutes Post Inhalation | 46.365 Percent ((FEV1/FVC)*100) STANDARD_DEVIATION 8.824 |
| Forced Expiratory Volume in 1 Second 0 Minutes Pre Inhalation | 1.1584 Liter STANDARD_DEVIATION 0.35206 |
| Forced Expiratory Volume in 1 Second 60 Minutes Post Inhalation | 1.3987 Liter STANDARD_DEVIATION 0.37266 |
| Forced Vital Capacity 0 Minutes Pre Inhalation | 2.7426 Liter STANDARD_DEVIATION 0.73932 |
| Forced Vital Capacity 60 Minutes Post Inhalation | 3.0781 Liter STANDARD_DEVIATION 0.81113 |
| Percent Predicted FEV1 0 Minutes Pre Inhalation | 43.90 Percent STANDARD_DEVIATION 10.873 |
| Percent Predicted FEV1 60 Minutes Post Inhalation | 53.10 Percent STANDARD_DEVIATION 11.68 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Reversibility | 9.19 Percent STANDARD_DEVIATION 4.743 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 31 |
| other Total, other adverse events | 5 / 31 | 3 / 31 |
| serious Total, serious adverse events | 0 / 31 | 2 / 31 |
Outcome results
Primary
Global Ventilated Lung Volume
The global distribution of inhaled gas within the lung was assessed using an inhaled gaseous contrast agent, Hyperpolarized Helium (3He) Lung Imaging. The Global Ventilated Lung Volume was expressed in percentage (%VV) of total lung volume.
Time frame: Day 8 to Day 10 (each treatment period)
Population: The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| QVA149 110/50 mcg | Global Ventilated Lung Volume | 61.73 Percentage of total lung volume |
| Matching Placebo | Global Ventilated Lung Volume | 56.73 Percentage of total lung volume |
Comparison: Global Ventilated Lung Volumep-value: 0.025490% CI: [1.4, 8.6]t-test, 2 sided
Secondary
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
The diffusing capacity of the lung for carbon monoxide (DLCO) is a measure of how easily carbon monoxide (CO) molecules transfer from the alveolar gas to the hemoglobin of the red cells in the pulmonary circulation. To measure the DLCO, the patient inhales a single breath containing a minute amount of CO and holds it for 10 seconds. The breath is then exhaled and the exhaled breath is analyzed for CO. The change in the concentration of the CO is then multiplied by the single breath TLC to calculate the DLCO.
Time frame: Day 8 (each treatment period)
Population: The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| QVA149 110/50 mcg | Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | 16.38 mL/min/mmHg |
| Matching Placebo | Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | 15.73 mL/min/mmHg |
Comparison: Diffusion Capacity of Lung for COp-value: 0.082190% CI: [0.04, 1.27]t-test, 2 sided
Secondary
FEV1/FVC Ratio
The FEV1/FVC ratio is the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC). The result of this ratio is expressed as FEV1%.
Time frame: Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period)
Population: The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| QVA149 110/50 mcg | FEV1/FVC Ratio | FEV1/FVC Day 1 (0.25 hrs post-dose) | 44.31 FEV1 Percentage |
| QVA149 110/50 mcg | FEV1/FVC Ratio | FEV1/FVC Day 1 (1 hrs post-dose) | 44.97 FEV1 Percentage |
| QVA149 110/50 mcg | FEV1/FVC Ratio | FEV1/FVC Day 1 (2 hrs post-dose) | 45.25 FEV1 Percentage |
| QVA149 110/50 mcg | FEV1/FVC Ratio | FEV1/FVC Day 8 (-0.75 hrs post-dose) | 45.05 FEV1 Percentage |
| QVA149 110/50 mcg | FEV1/FVC Ratio | FEV1/FVC Day 8 (-0.25 hrs post-dose) | 45.97 FEV1 Percentage |
| QVA149 110/50 mcg | FEV1/FVC Ratio | FEV1/FVC Day 8 (0.25 hrs post-dose) | 46.34 FEV1 Percentage |
| QVA149 110/50 mcg | FEV1/FVC Ratio | FEV1/FVC Day 8 (1 hrs post-dose) | 47.32 FEV1 Percentage |
| QVA149 110/50 mcg | FEV1/FVC Ratio | FEV1/FVC Day 8 (2 hrs post-dose) | 47.39 FEV1 Percentage |
| Matching Placebo | FEV1/FVC Ratio | FEV1/FVC Day 8 (2 hrs post-dose) | 42.42 FEV1 Percentage |
| Matching Placebo | FEV1/FVC Ratio | FEV1/FVC Day 1 (0.25 hrs post-dose) | 42.14 FEV1 Percentage |
| Matching Placebo | FEV1/FVC Ratio | FEV1/FVC Day 8 (-0.25 hrs post-dose) | 42.17 FEV1 Percentage |
| Matching Placebo | FEV1/FVC Ratio | FEV1/FVC Day 1 (1 hrs post-dose) | 42.91 FEV1 Percentage |
| Matching Placebo | FEV1/FVC Ratio | FEV1/FVC Day 8 (1 hrs post-dose) | 42.72 FEV1 Percentage |
| Matching Placebo | FEV1/FVC Ratio | FEV1/FVC Day 1 (2 hrs post-dose) | 42.93 FEV1 Percentage |
| Matching Placebo | FEV1/FVC Ratio | FEV1/FVC Day 8 (0.25 hrs post-dose) | 42.60 FEV1 Percentage |
| Matching Placebo | FEV1/FVC Ratio | FEV1/FVC Day 8 (-0.75 hrs post-dose) | 42.23 FEV1 Percentage |
Comparison: FEV1/FVC Day 8 (-0.25 hrs post-dose)p-value: <0.000190% CI: [2.51, 5.09]t-test, 2 sided
Comparison: FEV1/FVC Day 8 (0.25 hrs post-dose)p-value: <0.000190% CI: [2.45, 5.02]t-test, 2 sided
Comparison: FEV1/FVC Day 1 (0.25 hrs post-dose)p-value: 0.000690% CI: [1.21, 3.12]t-test, 2 sided
Comparison: FEV1/FVC Day 1 (1 hrs post-dose)p-value: 0.010690% CI: [0.78, 3.33]t-test, 2 sided
Comparison: FEV1/FVC Day 1 (2 hrs post-dose)p-value: 0.001390% CI: [1.2, 3.44]t-test, 2 sided
Comparison: FEV1/FVC Day 8 (-0.75 hrs post-dose)p-value: 0.001790% CI: [1.41, 4.23]t-test, 2 sided
Comparison: FEV1/FVC Day 8 (1 hrs post-dose)p-value: <0.000190% CI: [3.16, 6.03]t-test, 2 sided
Comparison: FEV1/FVC Day 8 (2 hrs post-dose)p-value: <0.000190% CI: [3.56, 6.39]t-test, 2 sided
Secondary
Forced Expiratory Volume in 1 Second (FEV1)
The Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.
Time frame: Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period)
Population: The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| QVA149 110/50 mcg | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 1 (0.25 hrs post-dose) | 1.27 Liter |
| QVA149 110/50 mcg | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 1 (1 hrs post-dose) | 1.32 Liter |
| QVA149 110/50 mcg | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 1 (2 hrs post-dose) | 1.34 Liter |
| QVA149 110/50 mcg | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (-0.75 hrs post-dose) | 1.30 Liter |
| QVA149 110/50 mcg | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (-0.25 hrs post-dose) | 1.33 Liter |
| QVA149 110/50 mcg | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (0.25 hrs post-dose) | 1.38 Liter |
| QVA149 110/50 mcg | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (1 hrs post-dose) | 1.45 Liter |
| QVA149 110/50 mcg | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (2 hrs post-dose) | 1.43 Liter |
| Matching Placebo | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (2 hrs post-dose) | 1.11 Liter |
| Matching Placebo | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 1 (0.25 hrs post-dose) | 1.13 Liter |
| Matching Placebo | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (-0.25 hrs post-dose) | 1.11 Liter |
| Matching Placebo | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 1 (1 hrs post-dose) | 1.12 Liter |
| Matching Placebo | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (1 hrs post-dose) | 1.13 Liter |
| Matching Placebo | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 1 (2 hrs post-dose) | 1.15 Liter |
| Matching Placebo | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (0.25 hrs post-dose) | 1.10 Liter |
| Matching Placebo | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 Day 8 (-0.75 hrs post-dose) | 1.09 Liter |
Comparison: FEV1 Day 1 (0.25 hrs post-dose)p-value: <0.000190% CI: [0.11, 0.18]t-test, 2 sided
Comparison: FEV1 Day 1 (1 hrs post-dose)p-value: <0.000190% CI: [0.15, 0.25]t-test, 2 sided
Comparison: FEV1 Day 1 (2 hrs post-dose)p-value: <0.000190% CI: [0.13, 0.24]t-test, 2 sided
Comparison: FEV1 Day 8 (-0.75 hrs post-dose)p-value: <0.000190% CI: [0.16, 0.27]t-test, 2 sided
Comparison: FEV1 Day 8 (-0.25 hrs post-dose)p-value: <0.000190% CI: [0.16, 0.28]t-test, 2 sided
Comparison: FEV1 Day 8 (0.25 hrs post-dose)p-value: <0.000190% CI: [0.23, 0.33]t-test, 2 sided
Comparison: FEV1 Day 8 (1 hrs post-dose)p-value: <0.000190% CI: [0.26, 0.37]t-test, 2 sided
Comparison: FEV1 Day 8 (2 hrs post-dose)p-value: <0.000190% CI: [0.26, 0.38]t-test, 2 sided
Secondary
Forced Vital Capacity (FVC)
Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. An increase in FVC indicates improvement in lung function.
Time frame: Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period)
Population: The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| QVA149 110/50 mcg | Forced Vital Capacity (FVC) | FVC Day 1 (0.25 hrs post-dose) | 2.92 Liter |
| QVA149 110/50 mcg | Forced Vital Capacity (FVC) | FVC Day 1 (1 hrs post-dose) | 2.99 Liter |
| QVA149 110/50 mcg | Forced Vital Capacity (FVC) | FVC Day 1 (2 hrs post-dose) | 2.99 Liter |
| QVA149 110/50 mcg | Forced Vital Capacity (FVC) | FVC Day 8 (-0.75 hrs post-dose) | 2.91 Liter |
| QVA149 110/50 mcg | Forced Vital Capacity (FVC) | FVC Day 8 (-0.25 hrs post-dose) | 2.91 Liter |
| QVA149 110/50 mcg | Forced Vital Capacity (FVC) | FVC Day 8 (0.25 hrs post-dose) | 3.02 Liter |
| QVA149 110/50 mcg | Forced Vital Capacity (FVC) | FVC Day 8 (1 hrs post-dose) | 3.10 Liter |
| QVA149 110/50 mcg | Forced Vital Capacity (FVC) | FVC Day 8 (2 hrs post-dose) | 3.06 Liter |
| Matching Placebo | Forced Vital Capacity (FVC) | FVC Day 8 (2 hrs post-dose) | 2.62 Liter |
| Matching Placebo | Forced Vital Capacity (FVC) | FVC Day 1 (0.25 hrs post-dose) | 2.68 Liter |
| Matching Placebo | Forced Vital Capacity (FVC) | FVC Day 8 (-0.25 hrs post-dose) | 2.63 Liter |
| Matching Placebo | Forced Vital Capacity (FVC) | FVC Day 1 (1 hrs post-dose) | 2.63 Liter |
| Matching Placebo | Forced Vital Capacity (FVC) | FVC Day 8 (1 hrs post-dose) | 2.65 Liter |
| Matching Placebo | Forced Vital Capacity (FVC) | FVC Day 1 (2 hrs post-dose) | 2.68 Liter |
| Matching Placebo | Forced Vital Capacity (FVC) | FVC Day 8 (0.25 hrs post-dose) | 2.59 Liter |
| Matching Placebo | Forced Vital Capacity (FVC) | FVC Day 8 (-0.75 hrs post-dose) | 2.56 Liter |
Comparison: FVC Day 1 (0.25 hrs post-dose)p-value: <0.000190% CI: [0.15, 0.33]t-test, 2 sided
Comparison: FVC Day 1 (1 hrs post-dose)p-value: <0.000190% CI: [0.25, 0.45]t-test, 2 sided
Comparison: FVC Day 1 (2 hrs post-dose)p-value: <0.000190% CI: [0.2, 0.42]t-test, 2 sided
Comparison: FVC Day 8 (-0.75 hrs post-dose)p-value: <0.00190% CI: [0.25, 0.45]t-test, 2 sided
Comparison: FVC Day 8 (-0.25 hrs post-dose)p-value: <0.000190% CI: [0.19, 0.37]t-test, 2 sided
Comparison: FVC Day 8 (0.25 hrs post-dose)p-value: <0.000190% CI: [0.33, 0.53]t-test, 2 sided
Comparison: FVC Day 8 (1 hrs post-dose)p-value: <0.000190% CI: [0.36, 0.54]t-test, 2 sided
Comparison: FVC Day 8 (2 hrs post-dose)p-value: <0.000190% CI: [0.33, 0.55]t-test, 2 sided
Secondary
Lung Clearance Index by Multiple Breath Nitrogen Washout (MBNW)
Multiple Breath Nitrogen Washout (MBNW) was performed after 2 hours post-dose spirometry assessments using a multiple breath inert gas washout technique. The device provides the global index of ventilation inhomogeneity assessment (LCI = Cumulative Expired Volume/Functional Residual Capacity).
Time frame: Day 8 (each treatment period)
Population: The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| QVA149 110/50 mcg | Lung Clearance Index by Multiple Breath Nitrogen Washout (MBNW) | 10.80 Ratio |
| Matching Placebo | Lung Clearance Index by Multiple Breath Nitrogen Washout (MBNW) | 10.81 Ratio |
Comparison: Lung Clearance Indexp-value: 0.98290% CI: [-0.62, 0.6]t-test, 2 sided
Secondary
Pulmonary Perfusion
Lung Perfusion Imaging, or MR perfusion imaging of the lung with gadolinium contrast agent, was performed to determine whether vascular abnormalities producing perfusion deficits corresponded to abnormalities in ventilation (hypoxic vasoconstriction). Pulmonary Perfusion was expressed in ml/100 g lung tissue/min of each lobar region.
Time frame: Day 8 to Day 10 (each treatment period)
Population: The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| QVA149 110/50 mcg | Pulmonary Perfusion | Lung Perfusion | 13.96 ml/100 g lung tissue/min |
| QVA149 110/50 mcg | Pulmonary Perfusion | Lung, Left Perfusion | 14.42 ml/100 g lung tissue/min |
| QVA149 110/50 mcg | Pulmonary Perfusion | Lung, Left Lower Lobe Perfusion | 13.48 ml/100 g lung tissue/min |
| QVA149 110/50 mcg | Pulmonary Perfusion | Lung, Left Upper Lobe Perfusion | 15.35 ml/100 g lung tissue/min |
| QVA149 110/50 mcg | Pulmonary Perfusion | Lung, Right Perfusion | 13.54 ml/100 g lung tissue/min |
| QVA149 110/50 mcg | Pulmonary Perfusion | Lung, Right Lower Lobe Perfusion | 13.26 ml/100 g lung tissue/min |
| QVA149 110/50 mcg | Pulmonary Perfusion | Lung, Right Middle Lobe Perfusion | 14.86 ml/100 g lung tissue/min |
| QVA149 110/50 mcg | Pulmonary Perfusion | Lung, Right Upper Lobe Perfusion | 13.57 ml/100 g lung tissue/min |
| Matching Placebo | Pulmonary Perfusion | Lung, Right Upper Lobe Perfusion | 12.70 ml/100 g lung tissue/min |
| Matching Placebo | Pulmonary Perfusion | Lung Perfusion | 13.03 ml/100 g lung tissue/min |
| Matching Placebo | Pulmonary Perfusion | Lung, Right Perfusion | 12.97 ml/100 g lung tissue/min |
| Matching Placebo | Pulmonary Perfusion | Lung, Left Perfusion | 13.08 ml/100 g lung tissue/min |
| Matching Placebo | Pulmonary Perfusion | Lung, Right Middle Lobe Perfusion | 13.36 ml/100 g lung tissue/min |
| Matching Placebo | Pulmonary Perfusion | Lung, Left Lower Lobe Perfusion | 12.79 ml/100 g lung tissue/min |
| Matching Placebo | Pulmonary Perfusion | Lung, Right Lower Lobe Perfusion | 13.25 ml/100 g lung tissue/min |
| Matching Placebo | Pulmonary Perfusion | Lung, Left Upper Lobe Perfusion | 13.45 ml/100 g lung tissue/min |
Comparison: Lung Perfusionp-value: 0.32390% CI: [-0.64, 2.5]t-test, 2 sided
Comparison: Lung, Left Perfusionp-value: 0.171790% CI: [-0.29, 2.97]t-test, 2 sided
Comparison: Lung, Left Lower Lobe Perfusionp-value: 0.503190% CI: [-1.05, 2.43]t-test, 2 sided
Comparison: Lung, Left Upper Lobe Perfusionp-value: 0.07690% CI: [0.15, 3.65]t-test, 2 sided
Comparison: Lung, Right Perfusionp-value: 0.546590% CI: [-1.02, 2.16]t-test, 2 sided
Comparison: Lung, Right Lower Lobe Perfusionp-value: 0.991390% CI: [-1.85, 1.87]t-test, 2 sided
Comparison: Lung, Right Middle Lobe Perfusionp-value: 0.383790% CI: [-1.39, 4.4]t-test, 2 sided
Comparison: Lung, Right Upper Lobe Perfusionp-value: 0.362490% CI: [-0.73, 2.48]t-test, 2 sided
Secondary
Regional Ventilated Lung Volume
The regional distribution of inhaled gas within the lung was assessed using an inhaled gaseous contrast agent, Hyperpolarized Helium (3He) Lung Imaging. The Regional Ventilated Lung Volume was expressed in percentage (% VDV) of total lung volume for each lobar region.
Time frame: Day 8 to Day 10 (each treatment period)
Population: The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| QVA149 110/50 mcg | Regional Ventilated Lung Volume | Lung, Left Upper Lobe Ventilation | 64.17 Percentage of total lung volume |
| QVA149 110/50 mcg | Regional Ventilated Lung Volume | Lung, Right Lower Lobe Ventilation | 60.92 Percentage of total lung volume |
| QVA149 110/50 mcg | Regional Ventilated Lung Volume | Lung, Left Lower Lobe Ventilation | 58.97 Percentage of total lung volume |
| QVA149 110/50 mcg | Regional Ventilated Lung Volume | Lung, Right Middle Lobe Ventilation | 59.59 Percentage of total lung volume |
| QVA149 110/50 mcg | Regional Ventilated Lung Volume | Lung, Right Ventilation | 61.63 Percentage of total lung volume |
| QVA149 110/50 mcg | Regional Ventilated Lung Volume | Lung, Right Upper Lobe Ventilation | 63.25 Percentage of total lung volume |
| QVA149 110/50 mcg | Regional Ventilated Lung Volume | Lung, Left Ventilation | 61.94 Percentage of total lung volume |
| Matching Placebo | Regional Ventilated Lung Volume | Lung, Right Upper Lobe Ventilation | 55.53 Percentage of total lung volume |
| Matching Placebo | Regional Ventilated Lung Volume | Lung, Left Ventilation | 57.16 Percentage of total lung volume |
| Matching Placebo | Regional Ventilated Lung Volume | Lung, Left Lower Lobe Ventilation | 54.01 Percentage of total lung volume |
| Matching Placebo | Regional Ventilated Lung Volume | Lung, Left Upper Lobe Ventilation | 59.20 Percentage of total lung volume |
| Matching Placebo | Regional Ventilated Lung Volume | Lung, Right Ventilation | 56.24 Percentage of total lung volume |
| Matching Placebo | Regional Ventilated Lung Volume | Lung, Right Lower Lobe Ventilation | 57.65 Percentage of total lung volume |
| Matching Placebo | Regional Ventilated Lung Volume | Lung, Right Middle Lobe Ventilation | 53.98 Percentage of total lung volume |
Comparison: Lung, Left Ventilationp-value: 0.03590% CI: [1.11, 8.44]t-test, 2 sided
Comparison: Lung, Left Lower Lobe Ventilationp-value: 0.094690% CI: [0.08, 9.84]t-test, 2 sided
Comparison: Lung, Left Upper Lobe Ventilationp-value: 0.048690% CI: [0.87, 9.07]t-test, 2 sided
Comparison: Lung, Right Ventilationp-value: 0.028690% CI: [1.42, 9.35]t-test, 2 sided
Comparison: Lung, Right Lower Lobe Ventilationp-value: 0.16590% CI: [-0.63, 7.17]t-test, 2 sided
Comparison: Lung, Right Middle Lobe Ventilationp-value: 0.142190% CI: [-0.71, 11.94]t-test, 2 sided
Comparison: Lung, Right Upper Lobe Ventilationp-value: 0.009990% CI: [2.98, 12.47]t-test, 2 sided