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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-004461-13 | EudraCT Number |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| QVA149 110/50 mcg then Matching placebo | Experimental | Single daily dose of 110/50 μg QVA149 for 8-10 days. |
|
| Matching placebo then QVA149 110/50 mcg | Placebo Comparator | Single daily dose of matching placebo for 8-10 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| QVA149 | Drug | QVA149 110/50 μg o.d. capsules for inhalation, supplied in blisters via the Concept 1 inhalation device, a single dose dry powder inhaler. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 8 to Day 10 (each treatment period) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 8 to Day 10 (each treatment period) |
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Sheffield | South Yorkshire | S10 2JF | United Kingdom | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35144620 | Derived | Singh D, Wild JM, Saralaya D, Lawson R, Marshall H, Goldin J, Brown MS, Kostikas K, Belmore K, Fogel R, Patalano F, Drollmann A, Machineni S, Jones I, Yates D, Tillmann HC. Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial. Respir Res. 2022 Feb 10;23(1):26. doi: 10.1186/s12931-022-01949-3. |
| Label | URL |
|---|---|
| A Plain Language Trial Summary is available on novartisclinicatrials.com | View source |
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31 patients were randomized, all of whom were included in the safety set and PD analysis sets (primary population of interest)
The study took place in 3 clinical sites in United-Kingdom
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| ID | Title | Description |
|---|---|---|
| FG000 | QVA149 110/50 mcg Then Matching Placebo | QVA149, followed by matching placebo. Each treatment 8-10 days. |
| FG001 | Matching Placebo Then QVA149 110/50 mcg | Matching placebo, followed by QVA149. Each treatment 8-10 days. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period One (First Treatment, 8-10 Days) |
| |||||||||||||
| Washout (Approximately 7-14 Days) |
| |||||||||||||
| Period 2 (Second Treatment, 8-10 Days) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants who were randomized to receive either QVA149 110/50 mcg or Placebo matching QVA149 110/50 mcg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered. | Posted | Least Squares Mean | 90% Confidence Interval | Percentage of total lung volume | Day 8 to Day 10 (each treatment period) |
|
Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 1 year.
Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events fields "number of deaths resulting from adverse events" all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | QVA149 110/50 mcg | Single daily dose of 110/50 μg QVA149 for 8-10 days. | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA (20.1) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | MedDRA (20.1) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 | Novartis.email@novartis.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 17, 2017 | Sep 25, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 13, 2016 | Sep 25, 2018 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D016540 | Smoking Cessation |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
Not provided
Not provided
| ID | Term |
|---|---|
| C554862 | indacaterol-glycopyrronium combination |
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| Placebo | Drug | Matching placebo |
|
| 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. |
| Day 8 to Day 10 (each treatment period) |
| 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. | 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) | 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. | 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) |
| 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%. | 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) |
| 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). | Day 8 (each treatment period) |
| 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. | Day 8 (each treatment period) |
| Bradford |
| West Yorkshire |
| BD9 6RJ |
| United Kingdom |
| Novartis Investigative Site | Manchester | M23 9QZ | United Kingdom |
| NOT COMPLETED |
|
| NOT COMPLETED |
|
|
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Forced Expiratory Volume in 1 Second | Spirometry assessments are to be performed 60 minutes post short-acting β2-adrenergic agonist (SABA) and short-acting muscarinic antagonist (SAMA) inhalation as part of the Baseline assessments. 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. | Mean | Standard Deviation | Liter |
|
| Percent Predicted FEV1 | Spirometry assessments are to be performed 60 minutes post short-acting β2-adrenergic agonist (SABA) and short-acting muscarinic antagonist (SAMA) inhalation as part of the Baseline assessments. | Mean | Standard Deviation | Percent |
|
| Forced Vital Capacity | Spirometry assessments are to be performed 60 minutes post short-acting β2-adrenergic agonist (SABA) and short-acting muscarinic antagonist (SAMA) inhalation as part of the Baseline assessments. 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. | Mean | Standard Deviation | Liter |
|
| FEV1/FVC ratio | Spirometry assessments are to be performed 60 minutes post short-acting β2-adrenergic agonist (SABA) and short-acting muscarinic antagonist (SAMA) inhalation as part of the Baseline assessments. 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). | Mean | Standard Deviation | Percent ((FEV1/FVC)*100) |
|
| Reversibility | Reversibility = FEV1 post-inhalation - FEV1 pre-inhalation. Reversibility was reported in absolute FEV1 values pre- and post-bronchodilator. | Mean | Standard Deviation | Liter |
|
| Reversibility | Reversibility = FEV1 post-inhalation - FEV1 pre-inhalation. Reversibility was reported in change in FEV1 between pre- and postbronchodilator assessment expressed in % of pre-bronchodilator FEV1. | Mean | Standard Deviation | Percent |
|
Single daily dose of matching placebo for 8-10 days.
|
|
|
| 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. | The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered. | Posted | Least Squares Mean | 90% Confidence Interval | Percentage of total lung volume | Day 8 to Day 10 (each treatment period) |
|
|
|
|
| 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. | The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered. | Posted | Least Squares Mean | 90% Confidence Interval | ml/100 g lung tissue/min | Day 8 to Day 10 (each treatment period) |
|
|
|
|
| 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. | The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered. | Posted | Least Squares Mean | 90% Confidence Interval | Liter | 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) |
|
|
|
|
| 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. | The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered. | Posted | Least Squares Mean | 90% Confidence Interval | Liter | 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) |
|
|
|
|
| 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%. | The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered. | Posted | Least Squares Mean | 90% Confidence Interval | FEV1 Percentage | 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) |
|
|
|
|
| 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). | The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered. | Posted | Least Squares Mean | 90% Confidence Interval | Ratio | Day 8 (each treatment period) |
|
|
|
|
| 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. | The PD Analysis Set, which consisted of all participants with valid results assessed in each treatment period, was considered. | Posted | Least Squares Mean | 90% Confidence Interval | mL/min/mmHg | Day 8 (each treatment period) |
|
|
|
|
| 31 |
| 0 |
| 31 |
| 5 |
| 31 |
| EG001 | Matching Placebo | Single daily dose of matching placebo for 8-10 days. | 0 | 31 | 2 | 31 | 3 | 31 |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA (20.1) | Systematic Assessment |
|
| Facial pain | General disorders | MedDRA (20.1) | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (20.1) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA (20.1) | Systematic Assessment |
|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (20.1) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D015438 | Health Behavior |
| D001519 | Behavior |
| Lung, Left Upper Lobe Ventilation |
|
| Lung, Right Ventilation |
|
| Lung, Right Lower Lobe Ventilation |
|
| Lung, Right Middle Lobe Ventilation |
|
| Lung, Right Upper Lobe Ventilation |
|
Lung, Left Lower Lobe Ventilation |
| t-test, 2 sided |
| 0.0946 |
| Mean Difference (Final Values) |
| 4.96 |
| Standard Error of the Mean |
| 2.86 |
| 2-Sided |
| 90 |
| 0.08 |
| 9.84 |
| Non-Inferiority |
Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Left Upper Lobe Ventilation | t-test, 2 sided | 0.0486 | Mean Difference (Final Values) | 4.97 | Standard Error of the Mean | 2.41 | 2-Sided | 90 | 0.87 | 9.07 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Right Ventilation | t-test, 2 sided | 0.0286 | Mean Difference (Final Values) | 5.39 | Standard Error of the Mean | 2.33 | 2-Sided | 90 | 1.42 | 9.35 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Right Lower Lobe Ventilation | t-test, 2 sided | 0.1650 | Mean Difference (Final Values) | 3.27 | Standard Error of the Mean | 2.29 | 2-Sided | 90 | -0.63 | 7.17 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Right Middle Lobe Ventilation | t-test, 2 sided | 0.1421 | Mean Difference (Final Values) | 5.61 | Standard Error of the Mean | 3.71 | 2-Sided | 90 | -0.71 | 11.94 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Right Upper Lobe Ventilation | t-test, 2 sided | 0.0099 | Mean Difference (Final Values) | 7.73 | Standard Error of the Mean | 2.78 | 2-Sided | 90 | 2.98 | 12.47 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Left Lower Lobe Perfusion |
|
| Lung, Left Upper Lobe Perfusion |
|
| Lung, Right Perfusion |
|
| Lung, Right Lower Lobe Perfusion |
|
| Lung, Right Middle Lobe Perfusion |
|
| Lung, Right Upper Lobe Perfusion |
|
Lung, Left Perfusion |
| t-test, 2 sided |
| 0.1717 |
| Mean Difference (Final Values) |
| 1.34 |
| Standard Error of the Mean |
| 0.95 |
| 2-Sided |
| 90 |
| -0.29 |
| 2.97 |
| Non-Inferiority |
Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Left Lower Lobe Perfusion | t-test, 2 sided | 0.5031 | Mean Difference (Final Values) | 0.69 | Standard Error of the Mean | 1.02 | 2-Sided | 90 | -1.05 | 2.43 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Left Upper Lobe Perfusion | t-test, 2 sided | 0.0760 | Mean Difference (Final Values) | 1.90 | Standard Error of the Mean | 1.03 | 2-Sided | 90 | 0.15 | 3.65 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Right Perfusion | t-test, 2 sided | 0.5465 | Mean Difference (Final Values) | 0.57 | Standard Error of the Mean | 0.93 | 2-Sided | 90 | -1.02 | 2.16 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Right Lower Lobe Perfusion | t-test, 2 sided | 0.9913 | Mean Difference (Final Values) | 0.01 | Standard Error of the Mean | 1.08 | 2-Sided | 90 | -1.85 | 1.87 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Right Middle Lobe Perfusion | t-test, 2 sided | 0.3837 | Mean Difference (Final Values) | 1.51 | Standard Error of the Mean | 1.70 | 2-Sided | 90 | -1.39 | 4.40 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| Lung, Right Upper Lobe Perfusion | t-test, 2 sided | 0.3624 | Mean Difference (Final Values) | 0.87 | Standard Error of the Mean | 0.94 | 2-Sided | 90 | -0.73 | 2.48 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment as fixed factors and patient as random factor. |
| FEV1 Day 1 (1 hrs post-dose) |
|
|
| FEV1 Day 1 (2 hrs post-dose) |
|
|
| FEV1 Day 8 (-0.75 hrs post-dose) |
|
|
| FEV1 Day 8 (-0.25 hrs post-dose) |
|
|
| FEV1 Day 8 (0.25 hrs post-dose) |
|
|
| FEV1 Day 8 (1 hrs post-dose) |
|
|
| FEV1 Day 8 (2 hrs post-dose) |
|
|
| FEV1 Day 1 (1 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.20 | Standard Error of the Mean | 0.03 | 2-Sided | 90 | 0.15 | 0.25 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1 Day 1 (2 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.19 | Standard Error of the Mean | 0.03 | 2-Sided | 90 | 0.13 | 0.24 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1 Day 8 (-0.75 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.22 | Standard Error of the Mean | 0.03 | 2-Sided | 90 | 0.16 | 0.27 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1 Day 8 (-0.25 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.22 | Standard Error of the Mean | 0.03 | 2-Sided | 90 | 0.16 | 0.28 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1 Day 8 (0.25 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.28 | Standard Error of the Mean | 0.03 | 2-Sided | 90 | 0.23 | 0.33 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1 Day 8 (1 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.32 | Standard Error of the Mean | 0.03 | 2-Sided | 90 | 0.26 | 0.37 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1 Day 8 (2 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.32 | Standard Error of the Mean | 0.04 | 2-Sided | 90 | 0.26 | 0.38 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FVC Day 1 (1 hrs post-dose) |
|
|
| FVC Day 1 (2 hrs post-dose) |
|
|
| FVC Day 8 (-0.75 hrs post-dose) |
|
|
| FVC Day 8 (-0.25 hrs post-dose) |
|
|
| FVC Day 8 (0.25 hrs post-dose) |
|
|
| FVC Day 8 (1 hrs post-dose) |
|
|
| FVC Day 8 (2 hrs post-dose) |
|
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| FVC Day 1 (1 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.35 | Standard Error of the Mean | 0.06 | 2-Sided | 90 | 0.25 | 0.45 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FVC Day 1 (2 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.31 | Standard Error of the Mean | 0.07 | 2-Sided | 90 | 0.20 | 0.42 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FVC Day 8 (-0.75 hrs post-dose) | t-test, 2 sided | <0.001 | Mean Difference (Final Values) | 0.35 | Standard Error of the Mean | 0.06 | 2-Sided | 90 | 0.25 | 0.45 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FVC Day 8 (-0.25 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.28 | Standard Error of the Mean | 0.06 | 2-Sided | 90 | 0.19 | 0.37 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FVC Day 8 (0.25 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.43 | Standard Error of the Mean | 0.06 | 2-Sided | 90 | 0.33 | 0.53 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FVC Day 8 (1 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.45 | Standard Error of the Mean | 0.06 | 2-Sided | 90 | 0.36 | 0.54 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FVC Day 8 (2 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 0.44 | Standard Error of the Mean | 0.06 | 2-Sided | 90 | 0.33 | 0.55 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1/FVC Day 1 (1 hrs post-dose) |
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| FEV1/FVC Day 1 (2 hrs post-dose) |
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| FEV1/FVC Day 8 (-0.75 hrs post-dose) |
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| FEV1/FVC Day 8 (-0.25 hrs post-dose) |
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| FEV1/FVC Day 8 (0.25 hrs post-dose) |
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| FEV1/FVC Day 8 (1 hrs post-dose) |
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| FEV1/FVC Day 8 (2 hrs post-dose) |
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| FEV1/FVC Day 1 (1 hrs post-dose) | t-test, 2 sided | 0.0106 | Mean Difference (Final Values) | 2.06 | Standard Error of the Mean | 0.75 | 2-Sided | 90 | 0.78 | 3.33 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1/FVC Day 1 (2 hrs post-dose) | t-test, 2 sided | 0.0013 | Mean Difference (Final Values) | 2.32 | Standard Error of the Mean | 0.66 | 2-Sided | 90 | 1.20 | 3.44 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1/FVC Day 8 (-0.75 hrs post-dose) | t-test, 2 sided | 0.0017 | Mean Difference (Final Values) | 2.82 | Standard Error of the Mean | 0.83 | 2-Sided | 90 | 1.41 | 4.23 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1/FVC Day 8 (-0.25 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 3.80 | Standard Error of the Mean | 0.76 | 2-Sided | 90 | 2.51 | 5.09 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1/FVC Day 8 (0.25 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 3.74 | Standard Error of the Mean | 0.75 | 2-Sided | 90 | 2.45 | 5.02 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1/FVC Day 8 (1 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 4.60 | Standard Error of the Mean | 0.85 | 2-Sided | 90 | 3.16 | 6.03 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |
| FEV1/FVC Day 8 (2 hrs post-dose) | t-test, 2 sided | <0.0001 | Mean Difference (Final Values) | 4.98 | Standard Error of the Mean | 0.83 | 2-Sided | 90 | 3.56 | 6.39 | Non-Inferiority | Parameters were analyzed using mixed effects model including sequence, period, treatment, time and treatment*Day*time interaction term as fixed factors and patient factor as random factor. Day*time was repeated within each patient*period interaction and subject average baseline and period adjusted baseline were included as covariates. |