Chronic Obstructive Pulmonary Disease: COPD
Conditions
Keywords
Moderate to severe COPD patients are included, NVA, QAB
Brief summary
The study purpose is to evaluate the effect of QAB149 * NVA237 vs. QAB149 on static lung hyperinflation.
Detailed description
This is a multicenter, randomized, double-blinded, single-dose, cross-over, placebo-controlled study. The primary endpoint was chosen to demonstrate the superiority of a single-dose of the combined inhalation vs. the mono inhalation regarding the Inspiratory Capacity (IC) peak value. A total of 78 patients will be randomized to complete two visits with two single doses of treatment. Patients will be randomized in a cross-over manner. Treatment visits will be separated by a study medication wash-out period.Treatments will be administered in a blinded fashion. The patients will be male and female patients, ≥40 years of age, with a documented diagnosis of moderate or severe COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and \>10-pack years history of smoking, FEV1 \<80% and ≥30% of the predicted normal value.
Interventions
DRUGQAB149
Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI
DRUGPlacebo
Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI
DRUGNVA237
Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI
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
* Male and female patients, ≥40 years of age, with a documented diagnosis of moderate or severe COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and \>10-pack year history of smoking * FEV1 \<80% and ≥30% of the predicted normal value who have signed an informed consent form prior to the initiation of any study-related procedure
Exclusion criteria
* No COPD exacerbations within 6 weeks prior to dosing * No concomitant lung disease such as asthma * Nno requirement for long term oxygen treatment or history of lung reduction surgery * No medical conditions that would interfere with the performance of spirometry * No other medical condition that in the opinion of the investigator may cause the patient to be unsuitable for completion of the study or place the patient at potential risk form being in the study e.g. uncontrolled hypertension or unstable ischemic heart disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Inspiratory Capacity (IC) Peak Value | Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours | IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean at one of the post-dose measurements (30min, 60min, 120min, 180min and 240min). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in One Second (FEV1) | Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours | FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was at 30, 60, 120, 180, and 240 minutes post-dose. Spirometry equipment and performance of spirometric testing had to be in accordance with standards as outlined in the American Thoracic Society for the Standardization of Spirometry recommendations. The spirometry equipment used during the study had to meet or exceed these minimal ATS recommendations |
| Inspiratory Capacity (IC) | within 4h after dosing | During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured at 30, 60, 120, 180, and 240 minutes post-dose |
| Forced Volume Capacity (FVC) | Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours | FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time |
| Total Lung Capacity (TLC) | Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours | TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30, 60, 120, 180 and 240 minutes post dose |
| Airway Resistance (Raw) | Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours | Raw was measured with spirometry conducted according to internationally accepted standards. Raw was the mean of the measurements which were measured each at 30, 60, 120, 180 and 240 minutes |
Countries
Switzerland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sequence A QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff) | 39 |
| Sequence B QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo | 38 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 1 | 1 |
| Period 1 | Medical or ethical, noncompliance | 2 | 0 |
| Period 1 | Other | 0 | 1 |
| Period 1 | Patient request | 0 | 1 |
| Period 2 | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Sequence A | Sequence B | Total |
|---|---|---|---|
| Age, Continuous | 65.62 Years STANDARD_DEVIATION 9.247 | 64.18 Years STANDARD_DEVIATION 7.447 | 64.91 Years STANDARD_DEVIATION 8.383 |
| Sex: Female, Male Female | 14 Participants | 17 Participants | 31 Participants |
| Sex: Female, Male Male | 25 Participants | 21 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 39 | 3 / 38 |
| serious Total, serious adverse events | 0 / 39 | 0 / 38 |
Outcome results
Primary
Inspiratory Capacity (IC) Peak Value
IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean at one of the post-dose measurements (30min, 60min, 120min, 180min and 240min).
Time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A | Inspiratory Capacity (IC) Peak Value | Day 6 (n=36, 36) | 2.99 Liters | Standard Deviation 0.856 |
| Sequence A | Inspiratory Capacity (IC) Peak Value | Day 0 (n=38, 38) | 2.87 Liters | Standard Deviation 0.808 |
| Sequence B | Inspiratory Capacity (IC) Peak Value | Day 6 (n=36, 36) | 2.85 Liters | Standard Deviation 0.707 |
| Sequence B | Inspiratory Capacity (IC) Peak Value | Day 0 (n=38, 38) | 2.94 Liters | Standard Deviation 0.777 |
Secondary
Airway Resistance (Raw)
Raw was measured with spirometry conducted according to internationally accepted standards. Raw was the mean of the measurements which were measured each at 30, 60, 120, 180 and 240 minutes
Time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A | Airway Resistance (Raw) | Day (0) 3 hour post-dose | 5.07 cmH2O/l/s | Standard Deviation 2.528 |
| Sequence A | Airway Resistance (Raw) | Day (6) 3 hour post-dose | 4.30 cmH2O/l/s | Standard Deviation 2.161 |
| Sequence A | Airway Resistance (Raw) | Day (0) 1 hour post-dose | 5.19 cmH2O/l/s | Standard Deviation 2.561 |
| Sequence A | Airway Resistance (Raw) | Day (0) 30 min post-dose | 5.13 cmH2O/l/s | Standard Deviation 2.243 |
| Sequence A | Airway Resistance (Raw) | Day (0) 2 hour post-dose | 5.21 cmH2O/l/s | Standard Deviation 2.496 |
| Sequence A | Airway Resistance (Raw) | Day (0) 4 hour post-dose | 5.18 cmH2O/l/s | Standard Deviation 2.535 |
| Sequence A | Airway Resistance (Raw) | Day (6) 30 min post-dose | 4.73 cmH2O/l/s | Standard Deviation 2.54 |
| Sequence A | Airway Resistance (Raw) | Day (6) 1 hour post-dose | 4.47 cmH2O/l/s | Standard Deviation 2.323 |
| Sequence A | Airway Resistance (Raw) | Day (6) 2 hour post-dose | 4.31 cmH2O/l/s | Standard Deviation 2.119 |
| Sequence A | Airway Resistance (Raw) | Day (6) 4 hour post-dose | 4.30 cmH2O/l/s | Standard Deviation 2.17 |
| Sequence B | Airway Resistance (Raw) | Day (6) 1 hour post-dose | 4.97 cmH2O/l/s | Standard Deviation 1.861 |
| Sequence B | Airway Resistance (Raw) | Day (0) 3 hour post-dose | 4.53 cmH2O/l/s | Standard Deviation 1.748 |
| Sequence B | Airway Resistance (Raw) | Day (0) 4 hour post-dose | 4.48 cmH2O/l/s | Standard Deviation 1.866 |
| Sequence B | Airway Resistance (Raw) | Day (6) 3 hour post-dose | 4.77 cmH2O/l/s | Standard Deviation 1.989 |
| Sequence B | Airway Resistance (Raw) | Day (6) 4 hour post-dose | 4.78 cmH2O/l/s | Standard Deviation 1.939 |
| Sequence B | Airway Resistance (Raw) | Day (6) 30 min post-dose | 5.18 cmH2O/l/s | Standard Deviation 2.13 |
| Sequence B | Airway Resistance (Raw) | Day (0) 30 min post-dose | 4.74 cmH2O/l/s | Standard Deviation 1.81 |
| Sequence B | Airway Resistance (Raw) | Day (0) 1 hour post-dose | 4.61 cmH2O/l/s | Standard Deviation 1.881 |
| Sequence B | Airway Resistance (Raw) | Day (6) 2 hour post-dose | 4.71 cmH2O/l/s | Standard Deviation 1.822 |
| Sequence B | Airway Resistance (Raw) | Day (0) 2 hour post-dose | 4.43 cmH2O/l/s | Standard Deviation 1.849 |
Secondary
Forced Expiratory Volume in One Second (FEV1)
FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was at 30, 60, 120, 180, and 240 minutes post-dose. Spirometry equipment and performance of spirometric testing had to be in accordance with standards as outlined in the American Thoracic Society for the Standardization of Spirometry recommendations. The spirometry equipment used during the study had to meet or exceed these minimal ATS recommendations
Time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (0) 3 hour post-dose | 1.53 Liters | Standard Deviation 0.43 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (6) 30 min post-dose | 1.59 Liters | Standard Deviation 0.437 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (6) 4 hour post-dose | 1.64 Liters | Standard Deviation 0.473 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (6) 1 hour post-dose | 1.63 Liters | Standard Deviation 0.465 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (0) 30 min post-dose | 1.49 Liters | Standard Deviation 0.442 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (6) 2 hour post-dose | 1.66 Liters | Standard Deviation 0.462 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (0) 2 hour post-dose | 1.51 Liters | Standard Deviation 0.437 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (6) 3 hour post-dose | 1.65 Liters | Standard Deviation 0.455 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (0) 1 hour post-dose | 1.50 Liters | Standard Deviation 0.44 |
| Sequence A | Forced Expiratory Volume in One Second (FEV1) | Day (0) 4 hour post-dose | 1.53 Liters | Standard Deviation 0.434 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (6) 4 hour post-dose | 1.56 Liters | Standard Deviation 0.459 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (0) 2 hour post-dose | 1.60 Liters | Standard Deviation 0.506 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (0) 1 hour post-dose | 1.60 Liters | Standard Deviation 0.506 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (0) 3 hour post-dose | 1.59 Liters | Standard Deviation 0.5 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (0) 4 hour post-dose | 1.60 Liters | Standard Deviation 0.492 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (6) 30 min post-dose | 1.52 Liters | Standard Deviation 0.473 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (6) 1 hour post-dose | 1.53 Liters | Standard Deviation 0.463 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (6) 2 hour post-dose | 1.55 Liters | Standard Deviation 0.476 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (6) 3 hour post-dose | 1.56 Liters | Standard Deviation 0.47 |
| Sequence B | Forced Expiratory Volume in One Second (FEV1) | Day (0) 30 min post-dose | 1.57 Liters | Standard Deviation 0.505 |
Secondary
Forced Volume Capacity (FVC)
FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time
Time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A | Forced Volume Capacity (FVC) | Day (0) 30 min post-dose | 2.98 Liters | Standard Deviation 0.917 |
| Sequence A | Forced Volume Capacity (FVC) | Day (0) 1 hour post-dose | 3.00 Liters | Standard Deviation 0.966 |
| Sequence A | Forced Volume Capacity (FVC) | Day (0) 2 hour post-dose | 3.01 Liters | Standard Deviation 0.947 |
| Sequence A | Forced Volume Capacity (FVC) | Day (0) 3 hour post-dose | 3.08 Liters | Standard Deviation 0.946 |
| Sequence A | Forced Volume Capacity (FVC) | Day (0) 4 hour post-dose | 3.07 Liters | Standard Deviation 0.968 |
| Sequence A | Forced Volume Capacity (FVC) | Day (6) 30 min post-dose | 3.19 Liters | Standard Deviation 1.002 |
| Sequence A | Forced Volume Capacity (FVC) | Day (6) 1 hour post-dose | 3.25 Liters | Standard Deviation 1.047 |
| Sequence A | Forced Volume Capacity (FVC) | Day (6) 2 hour post-dose | 3.29 Liters | Standard Deviation 1.018 |
| Sequence A | Forced Volume Capacity (FVC) | Day (6) 3 hour post-dose | 3.32 Liters | Standard Deviation 1.003 |
| Sequence A | Forced Volume Capacity (FVC) | Day (6) 4 hour post-dose | 3.30 Liters | Standard Deviation 1.012 |
| Sequence B | Forced Volume Capacity (FVC) | Day (6) 2 hour post-dose | 2.99 Liters | Standard Deviation 0.754 |
| Sequence B | Forced Volume Capacity (FVC) | Day (0) 30 min post-dose | 3.00 Liters | Standard Deviation 0.839 |
| Sequence B | Forced Volume Capacity (FVC) | Day (6) 30 min post-dose | 2.96 Liters | Standard Deviation 0.788 |
| Sequence B | Forced Volume Capacity (FVC) | Day (0) 1 hour post-dose | 3.02 Liters | Standard Deviation 0.846 |
| Sequence B | Forced Volume Capacity (FVC) | Day (6) 4 hour post-dose | 2.96 Liters | Standard Deviation 0.797 |
| Sequence B | Forced Volume Capacity (FVC) | Day (0) 2 hour post-dose | 3.04 Liters | Standard Deviation 0.862 |
| Sequence B | Forced Volume Capacity (FVC) | Day (6) 1 hour post-dose | 2.97 Liters | Standard Deviation 0.807 |
| Sequence B | Forced Volume Capacity (FVC) | Day (0) 3 hour post-dose | 3.04 Liters | Standard Deviation 0.872 |
| Sequence B | Forced Volume Capacity (FVC) | Day (6) 3 hour post-dose | 2.98 Liters | Standard Deviation 0.794 |
| Sequence B | Forced Volume Capacity (FVC) | Day (0) 4 hour post-dose | 3.07 Liters | Standard Deviation 0.852 |
Secondary
Inspiratory Capacity (IC)
During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured at 30, 60, 120, 180, and 240 minutes post-dose
Time frame: within 4h after dosing
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A | Inspiratory Capacity (IC) | Day (0) 30 min post-dose | 2.67 Liters | Standard Deviation 0.771 |
| Sequence A | Inspiratory Capacity (IC) | Day (0) 1 hour post-dose | 2.67 Liters | Standard Deviation 0.799 |
| Sequence A | Inspiratory Capacity (IC) | Day (0) 2 hour post-dose | 2.69 Liters | Standard Deviation 0.803 |
| Sequence A | Inspiratory Capacity (IC) | Day (0) 3 hour post-dose | 2.74 Liters | Standard Deviation 0.811 |
| Sequence A | Inspiratory Capacity (IC) | Day (0) 4 hour post-dose | 2.74 Liters | Standard Deviation 0.823 |
| Sequence A | Inspiratory Capacity (IC) | Day (6) 30 min post-dose | 2.79 Liters | Standard Deviation 0.826 |
| Sequence A | Inspiratory Capacity (IC) | Day (6) 1 hour post-dose | 2.80 Liters | Standard Deviation 0.81 |
| Sequence A | Inspiratory Capacity (IC) | Day (6) 2 hour post-dose | 2.86 Liters | Standard Deviation 0.846 |
| Sequence A | Inspiratory Capacity (IC) | Day (6) 3 hour post-dose | 2.83 Liters | Standard Deviation 0.841 |
| Sequence A | Inspiratory Capacity (IC) | Day (6) 4 hour post-dose | 2.85 Liters | Standard Deviation 0.799 |
| Sequence B | Inspiratory Capacity (IC) | Day (6) 2 hour post-dose | 2.74 Liters | Standard Deviation 0.689 |
| Sequence B | Inspiratory Capacity (IC) | Day (0) 30 min post-dose | 2.75 Liters | Standard Deviation 0.751 |
| Sequence B | Inspiratory Capacity (IC) | Day (6) 30 min post-dose | 2.40 Liters | Standard Deviation 0.724 |
| Sequence B | Inspiratory Capacity (IC) | Day (0) 1 hour post-dose | 2.79 Liters | Standard Deviation 0.774 |
| Sequence B | Inspiratory Capacity (IC) | Day (6) 4 hour post-dose | 2.68 Liters | Standard Deviation 0.699 |
| Sequence B | Inspiratory Capacity (IC) | Day (0) 2 hour post-dose | 2.71 Liters | Standard Deviation 0.709 |
| Sequence B | Inspiratory Capacity (IC) | Day (6) 1 hour post-dose | 2.72 Liters | Standard Deviation 0.759 |
| Sequence B | Inspiratory Capacity (IC) | Day (0) 3 hour post-dose | 2.69 Liters | Standard Deviation 0.8 |
| Sequence B | Inspiratory Capacity (IC) | Day (6) 3 hour post-dose | 2.69 Liters | Standard Deviation 0.719 |
| Sequence B | Inspiratory Capacity (IC) | Day (0) 4 hour post-dose | 2.74 Liters | Standard Deviation 0.754 |
Secondary
Total Lung Capacity (TLC)
TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30, 60, 120, 180 and 240 minutes post dose
Time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sequence A | Total Lung Capacity (TLC) | Day (0) 30 min post-dose | 7.20 Liters | Standard Deviation 1.587 |
| Sequence A | Total Lung Capacity (TLC) | Day (0) 1 hour post-dose | 7.17 Liters | Standard Deviation 1.559 |
| Sequence A | Total Lung Capacity (TLC) | Day (0) 2 hour post-dose | 7.06 Liters | Standard Deviation 1.658 |
| Sequence A | Total Lung Capacity (TLC) | Day (0) 3 hour post-dose | 7.14 Liters | Standard Deviation 1.662 |
| Sequence A | Total Lung Capacity (TLC) | Day (0) 4 hour post-dose | 7.21 Liters | Standard Deviation 1.608 |
| Sequence A | Total Lung Capacity (TLC) | Day (6) 30 min post-dose | 7.20 Liters | Standard Deviation 1.664 |
| Sequence A | Total Lung Capacity (TLC) | Day (6) 1 hour post-dose | 7.12 Liters | Standard Deviation 1.576 |
| Sequence A | Total Lung Capacity (TLC) | Day (6) 2 hour post-dose | 7.21 Liters | Standard Deviation 1.641 |
| Sequence A | Total Lung Capacity (TLC) | Day (6) 3 hour post-dose | 7.23 Liters | Standard Deviation 1.561 |
| Sequence A | Total Lung Capacity (TLC) | Day (6) 4 hour post-dose | 7.30 Liters | Standard Deviation 1.691 |
| Sequence B | Total Lung Capacity (TLC) | Day (6) 2 hour post-dose | 6.80 Liters | Standard Deviation 1.213 |
| Sequence B | Total Lung Capacity (TLC) | Day (0) 30 min post-dose | 6.81 Liters | Standard Deviation 1.144 |
| Sequence B | Total Lung Capacity (TLC) | Day (6) 30 min post-dose | 6.79 Liters | Standard Deviation 1.243 |
| Sequence B | Total Lung Capacity (TLC) | Day (0) 1 hour post-dose | 6.79 Liters | Standard Deviation 1.197 |
| Sequence B | Total Lung Capacity (TLC) | Day (6) 4 hour post-dose | 6.93 Liters | Standard Deviation 1.376 |
| Sequence B | Total Lung Capacity (TLC) | Day (0) 2 hour post-dose | 6.81 Liters | Standard Deviation 1.19 |
| Sequence B | Total Lung Capacity (TLC) | Day (6) 1 hour post-dose | 6.80 Liters | Standard Deviation 1.312 |
| Sequence B | Total Lung Capacity (TLC) | Day (0) 3 hour post-dose | 6.82 Liters | Standard Deviation 1.198 |
| Sequence B | Total Lung Capacity (TLC) | Day (6) 3 hour post-dose | 6.81 Liters | Standard Deviation 1.304 |
| Sequence B | Total Lung Capacity (TLC) | Day (0) 4 hour post-dose | 6.78 Liters | Standard Deviation 1.247 |