Asthma
Conditions
Keywords
COPD
Brief summary
The purpose of this study is to evaluate the pharmacodynamics of single doses of inhaled LAS100977 QD in patients with persistent asthma.
Interventions
DRUGLAS100977 0.313 μg
Dry powder inhalation, once-daily, single-dose
DRUGLAS100977 0.625 μg
Dry powder inhalation, once-daily, single-dose
DRUGLAS100977 1.25 μg
Dry powder inhalation, once-daily, single-dose
DRUGLAS100977 2.5 μg
Dry powder inhalation, once-daily, single-dose
DRUGSalbutamol 400 μg
Pressurized inhalation suspension, once-daily, single-dose
DRUGSalbutamol placebo
Pressurized inhalation, once-daily
DRUGLAS100977 placebo
Dry powder inhalation, once-daily
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Adult male and female patients aged 18-70 years (both included). 2. Clinical diagnosis of persistent asthma (according to GINA guidelines 2009 update) for at least 6 months prior to screening. 3. Screening FEV1 value of 60% \< FEV1 ≤ 85% of the predicted normal value. 4. FEV1 reversibility ≥ 12% and an absolute increase of at least 200 ml over baseline value after inhalation of 400µg (four inhalations) of salbutamol. 5. Pre-dose FEV1 value of first treatment period within the range of ± 20% of the FEV1 measured at screening prior to salbutamol inhalation. 6. Patients on a stable dose and regimen
Exclusion criteria
1. Current smokers, former smokers within the last 6 months, or ex-smokers with a history of more than 10 pack-years. 2. Patients diagnosed with COPD. 3. Recent Respiratory tract infections within 6 weeks before Screening Visit. 4. Intubation (ever) or hospitalization for longer than 24 hours for the management of an asthma exacerbation within the preceding 6 weeks of the screening visit. 5. Clinically significant respiratory conditions. 6. Clinically significant cardiovascular conditions. 7. Patients unable to properly use a dry powder or pMDI inhaler device or unable to perform acceptable spirometry. 8. Clinically relevant abnormalities laboratory, ECG parameters or physical examination results at the screening evaluation that in the investigator's opinion, preclude study participation. 9. Patients who intend to use any concomitant medication not permitted by this protocol or who have not undergone the required washout period for a particular prohibited medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Forced Expiratory Volume in One Second (FEV1) | +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose | The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected. |
| Time to Peak Forced Expiratory Volume in One Second (FEV1) | +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose | The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected. |
| Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1) | Baseline and +23 h and +24 h post-dose | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). Trough at Day 2 was computed as the average of the two values measured at 23 and 24 hours after administration of the morning dose of investigational medicinal product on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. |
| Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1 | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h | FEV1 was normalized to baseline. Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. |
| Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. |
| Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown. |
| Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown. |
| Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected. |
| Peak Forced Vital Capacity (FVC) | +15 min, +30 min, +1 h, +2 h, +3 h, +4 h | The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. |
| Time to Peak Forced Vital Capacity (FVC) | +15 min, +30 min, +1 h, +2 h, +3 h, +4 h | The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. |
| Change From Baseline to Trough Forced Vital Capacity (FVC) | Baseline and +23 h +24 h post-dose | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). Trough at Day 2 was computed as the average of the two values measured at 23 and 24 hours after administration of the morning dose of investigational medicinal product on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. |
| Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC) | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h | FVC was normalized to baseline. Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. |
| Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown. |
| Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown. |
| Change From Baseline in Peak Forced Vital Capacity (FVC) | Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose | Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. |
Countries
Germany, United Kingdom
Participant flow
Recruitment details
The study was conducted in 10 sites in Germany and United Kingdom, 9 of which randomized patients
Pre-assignment details
Screening took place 12-16 days before randomization. After screening, eligible patients entered a run-in period to assess clinical stability. A total of 115 patients were screened; 62 patients were assessed as eligible and randomized; 53 were not randomized due to screening failure (primarily non-fulfillment of inclusion/exclusion criteria)
Participants by arm
| Arm | Count |
|---|---|
| Overall Population Safety population defined as all patients who were randomized and received at least one dose of investigational medicinal product | 62 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
| Period 3 | Stability criteria not fullfilled | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 4 | Not able to maintain visit schedule | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Overall Population |
|---|---|
| Age, Continuous | 40.9 Years STANDARD_DEVIATION 11.2 |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 40 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 59 | 12 / 60 | 10 / 60 | 12 / 60 | 9 / 61 | 6 / 62 |
| serious Total, serious adverse events | 0 / 59 | 0 / 60 | 0 / 60 | 0 / 60 | 0 / 61 | 0 / 62 |
Outcome results
Primary
Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Population: ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.202 Liters | Standard Error 0.045 |
| LAS100977 0.313 μg | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.477 Liters | Standard Error 0.045 |
| LAS100977 0.625 μg | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.524 Liters | Standard Error 0.045 |
| LAS100977 1.25 μg | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.573 Liters | Standard Error 0.045 |
| LAS100977 2.5 μg | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.608 Liters | Standard Error 0.045 |
| Salbutamol 400 μg | Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 0.555 Liters | Standard Error 0.045 |
p-value: <0.000195% CI: [0.353, 0.458]ANCOVA
p-value: <0.000195% CI: [0.318, 0.424]ANCOVA
p-value: <0.000195% CI: [0.269, 0.375]ANCOVA
p-value: <0.000195% CI: [0.221, 0.327]ANCOVA
Secondary
Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 2.696 Liters | Standard Error 0.03 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 2.719 Liters | Standard Error 0.037 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 2.746 Liters | Standard Error 0.039 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 2.771 Liters | Standard Error 0.041 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 2.774 Liters | Standard Error 0.044 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 2.722 Liters | Standard Error 0.038 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 2.715 Liters | Standard Error 0.04 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 2.659 Liters | Standard Error 0.044 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 2.597 Liters | Standard Error 0.042 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 2.588 Liters | Standard Error 0.04 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 2.618 Liters | Standard Error 0.04 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 2.689 Liters | Standard Error 0.042 |
| Placebo | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 2.723 Liters | Standard Error 0.034 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 3.034 Liters | Standard Error 0.038 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 2.956 Liters | Standard Error 0.033 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 2.863 Liters | Standard Error 0.03 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 2.943 Liters | Standard Error 0.043 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 2.840 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 3.008 Liters | Standard Error 0.038 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 3.000 Liters | Standard Error 0.037 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 2.903 Liters | Standard Error 0.041 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 2.823 Liters | Standard Error 0.041 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 2.804 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 3.058 Liters | Standard Error 0.044 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 3.033 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 3.069 Liters | Standard Error 0.041 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 3.062 Liters | Standard Error 0.039 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 2.972 Liters | Standard Error 0.033 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 2.980 Liters | Standard Error 0.043 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 3.102 Liters | Standard Error 0.041 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 3.081 Liters | Standard Error 0.038 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 2.886 Liters | Standard Error 0.03 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 3.124 Liters | Standard Error 0.044 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 3.025 Liters | Standard Error 0.037 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 2.890 Liters | Standard Error 0.04 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 3.087 Liters | Standard Error 0.038 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 2.798 Liters | Standard Error 0.041 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 2.836 Liters | Standard Error 0.04 |
| LAS100977 0.625 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 2.941 Liters | Standard Error 0.041 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 3.035 Liters | Standard Error 0.043 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 3.136 Liters | Standard Error 0.038 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 3.190 Liters | Standard Error 0.041 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 2.892 Liters | Standard Error 0.041 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 3.167 Liters | Standard Error 0.044 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 3.157 Liters | Standard Error 0.038 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 3.139 Liters | Standard Error 0.039 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 3.018 Liters | Standard Error 0.041 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 3.033 Liters | Standard Error 0.033 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 2.923 Liters | Standard Error 0.04 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 2.948 Liters | Standard Error 0.04 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 2.934 Liters | Standard Error 0.03 |
| LAS100977 1.25 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 3.098 Liters | Standard Error 0.037 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 3.094 Liters | Standard Error 0.042 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 3.194 Liters | Standard Error 0.038 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 3.188 Liters | Standard Error 0.039 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 2.985 Liters | Standard Error 0.04 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 3.089 Liters | Standard Error 0.033 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 2.929 Liters | Standard Error 0.041 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 3.133 Liters | Standard Error 0.037 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 3.019 Liters | Standard Error 0.04 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 3.211 Liters | Standard Error 0.044 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 3.007 Liters | Standard Error 0.03 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 3.111 Liters | Standard Error 0.043 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 3.180 Liters | Standard Error 0.039 |
| LAS100977 2.5 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 3.196 Liters | Standard Error 0.041 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 2.605 Liters | Standard Error 0.04 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 2.683 Liters | Standard Error 0.043 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 3.123 Liters | Standard Error 0.039 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 2.812 Liters | Standard Error 0.038 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 2.669 Liters | Standard Error 0.044 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 3.040 Liters | Standard Error 0.041 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 3.147 Liters | Standard Error 0.037 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 2.562 Liters | Standard Error 0.04 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 2.772 Liters | Standard Error 0.039 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 3.106 Liters | Standard Error 0.03 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 2.937 Liters | Standard Error 0.044 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 3.142 Liters | Standard Error 0.034 |
| Salbutamol 400 μg | Absolute Values of Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 2.690 Liters | Standard Error 0.041 |
Secondary
Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 4.320 Liters | Standard Error 0.032 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 4.238 Liters | Standard Error 0.038 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 4.325 Liters | Standard Error 0.035 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 4.321 Liters | Standard Error 0.034 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 4.252 Liters | Standard Error 0.04 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.25h | 4.295 Liters | Standard Error 0.03 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 4.235 Liters | Standard Error 0.036 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 4.295 Liters | Standard Error 0.034 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 4.322 Liters | Standard Error 0.033 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 4.352 Liters | Standard Error 0.036 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 4.310 Liters | Standard Error 0.036 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 4.244 Liters | Standard Error 0.037 |
| Placebo | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 4.316 Liters | Standard Error 0.035 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 4.359 Liters | Standard Error 0.037 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 4.366 Liters | Standard Error 0.036 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 4.413 Liters | Standard Error 0.033 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 4.458 Liters | Standard Error 0.032 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.25h | 4.420 Liters | Standard Error 0.03 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 4.390 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 4.442 Liters | Standard Error 0.034 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 4.459 Liters | Standard Error 0.035 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 4.357 Liters | Standard Error 0.036 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 4.445 Liters | Standard Error 0.034 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 4.409 Liters | Standard Error 0.036 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 4.462 Liters | Standard Error 0.035 |
| LAS100977 0.313 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 4.456 Liters | Standard Error 0.035 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 4.444 Liters | Standard Error 0.034 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.25h | 4.368 Liters | Standard Error 0.03 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 4.405 Liters | Standard Error 0.032 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 4.429 Liters | Standard Error 0.034 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 4.472 Liters | Standard Error 0.035 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 1.411 Liters | Standard Error 0.033 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 4.412 Liters | Standard Error 0.035 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 4.349 Liters | Standard Error 0.036 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 4.360 Liters | Standard Error 0.036 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 4.303 Liters | Standard Error 0.036 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 4.335 Liters | Standard Error 0.038 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 4.280 Liters | Standard Error 0.039 |
| LAS100977 0.625 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 4.462 Liters | Standard Error 0.035 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 4.487 Liters | Standard Error 0.035 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.25h | 4.383 Liters | Standard Error 0.03 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 4.414 Liters | Standard Error 0.036 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 4.495 Liters | Standard Error 0.034 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 4.436 Liters | Standard Error 0.036 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 4.375 Liters | Standard Error 0.036 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 4.480 Liters | Standard Error 0.034 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 4.384 Liters | Standard Error 0.038 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 4.352 Liters | Standard Error 0.039 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 4.438 Liters | Standard Error 0.032 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 4.464 Liters | Standard Error 0.033 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 4.463 Liters | Standard Error 0.035 |
| LAS100977 1.25 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 4.505 Liters | Standard Error 0.035 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 4.381 Liters | Standard Error 0.039 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 4.505 Liters | Standard Error 0.035 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 4.512 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 4.517 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 4.410 Liters | Standard Error 0.038 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 4.453 Liters | Standard Error 0.036 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 4.367 Liters | Standard Error 0.036 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 4.498 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 4.513 Liters | Standard Error 0.033 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 4.443 Liters | Standard Error 0.032 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 4.458 Liters | Standard Error 0.036 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.25h | 4.417 Liters | Standard Error 0.03 |
| LAS100977 2.5 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 4.499 Liters | Standard Error 0.035 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 4.360 Liters | Standard Error 0.033 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 4.223 Liters | Standard Error 0.037 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 4.193 Liters | Standard Error 0.038 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 4.502 Liters | Standard Error 0.032 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 4.277 Liters | Standard Error 0.037 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 4.454 Liters | Standard Error 0.036 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 4.284 Liters | Standard Error 0.04 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 4.335 Liters | Standard Error 0.035 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 0.25h | 4.471 Liters | Standard Error 0.03 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 4.502 Liters | Standard Error 0.034 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 4.477 Liters | Standard Error 0.034 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 4.269 Liters | Standard Error 0.037 |
| Salbutamol 400 μg | Absolute Values of Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 4.398 Liters | Standard Error 0.035 |
Secondary
Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 0.121 Liters | Standard Error 0.044 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 0.035 Liters | Standard Error 0.042 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 0.056 Liters | Standard Error 0.04 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | -0.067 Liters | Standard Error 0.04 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 0.094 Liters | Standard Error 0.039 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 0.067 Liters | Standard Error 0.038 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 0.071 Liters | Standard Error 0.034 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | -0.053 Liters | Standard Error 0.042 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | -0.040 Liters | Standard Error 0.04 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 0.005 Liters | Standard Error 0.044 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 0.119 Liters | Standard Error 0.041 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 0.067 Liters | Standard Error 0.037 |
| Placebo | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 0.048 Liters | Standard Error 0.03 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 0.348 Liters | Standard Error 0.037 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 0.353 Liters | Standard Error 0.038 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 0.406 Liters | Standard Error 0.044 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 0.304 Liters | Standard Error 0.033 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 0.214 Liters | Standard Error 0.03 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 0.169 Liters | Standard Error 0.041 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 0.183 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 0.374 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 0.148 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 0.382 Liters | Standard Error 0.038 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 0.253 Liters | Standard Error 0.041 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 0.288 Liters | Standard Error 0.043 |
| LAS100977 0.313 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 0.416 Liters | Standard Error 0.041 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 0.403 Liters | Standard Error 0.039 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 0.237 Liters | Standard Error 0.03 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 0.319 Liters | Standard Error 0.033 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 0.373 Liters | Standard Error 0.037 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 0.429 Liters | Standard Error 0.038 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 0.450 Liters | Standard Error 0.041 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 0.432 Liters | Standard Error 0.038 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 0.326 Liters | Standard Error 0.043 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 0.181 Liters | Standard Error 0.04 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 0.233 Liters | Standard Error 0.04 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 0.144 Liters | Standard Error 0.041 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 0.471 Liters | Standard Error 0.044 |
| LAS100977 0.625 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 0.291 Liters | Standard Error 0.041 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 0.381 Liters | Standard Error 0.033 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 0.380 Liters | Standard Error 0.043 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 0.515 Liters | Standard Error 0.044 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 0.484 Liters | Standard Error 0.038 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 0.501 Liters | Standard Error 0.038 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 0.367 Liters | Standard Error 0.041 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 0.446 Liters | Standard Error 0.037 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 0.291 Liters | Standard Error 0.04 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 0.268 Liters | Standard Error 0.04 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 0.537 Liters | Standard Error 0.041 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 0.285 Liters | Standard Error 0.03 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 0.480 Liters | Standard Error 0.039 |
| LAS100977 1.25 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 0.238 Liters | Standard Error 0.041 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 0.330 Liters | Standard Error 0.04 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 0.481 Liters | Standard Error 0.037 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 0.275 Liters | Standard Error 0.041 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 0.543 Liters | Standard Error 0.041 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 0.358 Liters | Standard Error 0.03 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 0.456 Liters | Standard Error 0.043 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 0.558 Liters | Standard Error 0.044 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 0.521 Liters | Standard Error 0.039 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 0.362 Liters | Standard Error 0.04 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 0.536 Liters | Standard Error 0.039 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 0.443 Liters | Standard Error 0.042 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 0.437 Liters | Standard Error 0.033 |
| LAS100977 2.5 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 0.539 Liters | Standard Error 0.038 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | -0.093 Liters | Standard Error 0.04 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 0.113 Liters | Standard Error 0.039 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 0.471 Liters | Standard Error 0.039 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 0.032 Liters | Standard Error 0.043 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 0.014 Liters | Standard Error 0.044 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 0.495 Liters | Standard Error 0.037 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 0.157 Liters | Standard Error 0.038 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 0.490 Liters | Standard Error 0.034 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | -0.052 Liters | Standard Error 0.04 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 0.457 Liters | Standard Error 0.03 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 0.036 Liters | Standard Error 0.041 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 0.284 Liters | Standard Error 0.044 |
| Salbutamol 400 μg | Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 0.388 Liters | Standard Error 0.041 |
Secondary
Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | -0.027 Liters | Standard Error 0.036 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 0.055 Liters | Standard Error 0.035 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 0.089 Liters | Standard Error 0.036 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 0.060 Liters | Standard Error 0.034 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | -0.034 Liters | Standard Error 0.038 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 0.034 Liters | Standard Error 0.034 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | -0.011 Liters | Standard Error 0.04 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | -0.022 Liters | Standard Error 0.037 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.25 hr | 0.038 Liters | Standard Error 0.03 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 0.059 Liters | Standard Error 0.032 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 0.042 Liters | Standard Error 0.036 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 0.054 Liters | Standard Error 0.035 |
| Placebo | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 0.057 Liters | Standard Error 0.033 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 0.086 Liters | Standard Error 0.037 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 0.184 Liters | Standard Error 0.034 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 0.199 Liters | Standard Error 0.035 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.25 hr | 0.162 Liters | Standard Error 0.03 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 0.141 Liters | Standard Error 0.036 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 0.197 Liters | Standard Error 0.032 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 0.095 Liters | Standard Error 0.036 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 0.198 Liters | Standard Error 0.035 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 0.128 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 0.182 Liters | Standard Error 0.034 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 0.185 Liters | Standard Error 0.035 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 0.101 Liters | Standard Error 0.036 |
| LAS100977 0.313 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 0.149 Liters | Standard Error 0.033 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 0.097 Liters | Standard Error 0.036 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.25 hr | 0.111 Liters | Standard Error 0.03 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 0.144 Liters | Standard Error 0.032 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 0.169 Liters | Standard Error 0.034 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 0.183 Liters | Standard Error 0.034 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 0.201 Liters | Standard Error 0.035 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 0.147 Liters | Standard Error 0.033 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 0.209 Liters | Standard Error 0.035 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 0.141 Liters | Standard Error 0.035 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 0.081 Liters | Standard Error 0.036 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 0.038 Liters | Standard Error 0.036 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 0.063 Liters | Standard Error 0.038 |
| LAS100977 0.625 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 0.018 Liters | Standard Error 0.039 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 0.110 Liters | Standard Error 0.036 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 0.089 Liters | Standard Error 0.039 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 0.111 Liters | Standard Error 0.038 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 0.177 Liters | Standard Error 0.032 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 0.234 Liters | Standard Error 0.034 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 0.216 Liters | Standard Error 0.035 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 0.241 Liters | Standard Error 0.035 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 0.202 Liters | Standard Error 0.035 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.25 hr | 0.125 Liters | Standard Error 0.03 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 0.146 Liters | Standard Error 0.036 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 0.200 Liters | Standard Error 0.033 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 0.173 Liters | Standard Error 0.036 |
| LAS100977 1.25 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 0.219 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 0.242 Liters | Standard Error 0.035 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 0.256 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 0.195 Liters | Standard Error 0.036 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 0.182 Liters | Standard Error 0.032 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 0.249 Liters | Standard Error 0.033 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 0.118 Liters | Standard Error 0.039 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | 0.137 Liters | Standard Error 0.038 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 0.237 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 0.185 Liters | Standard Error 0.036 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 0.252 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | 0.102 Liters | Standard Error 0.036 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.25 hr | 0.159 Liters | Standard Error 0.03 |
| LAS100977 2.5 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 0.228 Liters | Standard Error 0.035 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 36 hr | 0.022 Liters | Standard Error 0.04 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 3 hr | 0.191 Liters | Standard Error 0.036 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 14 hr | 0.006 Liters | Standard Error 0.037 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 4 hr | 0.137 Liters | Standard Error 0.035 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 6 hr | 0.096 Liters | Standard Error 0.033 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.25 hr | 0.213 Liters | Standard Error 0.03 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 8 hr | 0.064 Liters | Standard Error 0.035 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 12 hr | 0.001 Liters | Standard Error 0.037 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 1 hr | 0.242 Liters | Standard Error 0.034 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 23 hr | -0.043 Liters | Standard Error 0.037 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 0.5 hr | 0.241 Liters | Standard Error 0.032 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 2 hr | 0.217 Liters | Standard Error 0.034 |
| Salbutamol 400 μg | Change From Baseline in Forced Vital Capacity (FVC) at Each Timepoint | 24 hr | -0.079 Liters | Standard Error 0.038 |
Secondary
Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1
FEV1 was normalized to baseline. Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1 | 0.007 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1 | 0.282 Liters | Standard Error 0.039 |
| LAS100977 0.625 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1 | 0.321 Liters | Standard Error 0.038 |
| LAS100977 1.25 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1 | 0.390 Liters | Standard Error 0.038 |
| LAS100977 2.5 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1 | 0.446 Liters | Standard Error 0.039 |
| Salbutamol 400 μg | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-24h at Day 1 | 0.100 Liters | Standard Error 0.039 |
Secondary
Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC)
FVC was normalized to baseline. Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h and +24 h
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC) | 0.017 Liters | Standard Error 0.031 |
| LAS100977 0.313 μg | Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC) | 0.135 Liters | Standard Error 0.031 |
| LAS100977 0.625 μg | Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC) | 0.109 Liters | Standard Error 0.03 |
| LAS100977 1.25 μg | Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC) | 0.169 Liters | Standard Error 0.03 |
| LAS100977 2.5 μg | Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC) | 0.192 Liters | Standard Error 0.031 |
| Salbutamol 400 μg | Change From Baseline in Normalized Forced Vital Capacity (FVC) Area Under the Curve (AUC) | 0.054 Liters | Standard Error 0.031 |
Secondary
Change From Baseline in Peak Forced Vital Capacity (FVC)
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Population: ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Peak Forced Vital Capacity (FVC) | 0.222 Liters | Standard Error 0.034 |
| LAS100977 0.313 μg | Change From Baseline in Peak Forced Vital Capacity (FVC) | 0.317 Liters | Standard Error 0.034 |
| LAS100977 0.625 μg | Change From Baseline in Peak Forced Vital Capacity (FVC) | 0.329 Liters | Standard Error 0.034 |
| LAS100977 1.25 μg | Change From Baseline in Peak Forced Vital Capacity (FVC) | 0.361 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Change From Baseline in Peak Forced Vital Capacity (FVC) | 0.380 Liters | Standard Error 0.034 |
| Salbutamol 400 μg | Change From Baseline in Peak Forced Vital Capacity (FVC) | 0.361 Liters | Standard Error 0.034 |
Secondary
Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1)
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). Trough at Day 2 was computed as the average of the two values measured at 23 and 24 hours after administration of the morning dose of investigational medicinal product on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time frame: Baseline and +23 h and +24 h post-dose
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1) | -0.054 Liters | Standard Error 0.039 |
| LAS100977 0.313 μg | Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1) | 0.166 Liters | Standard Error 0.039 |
| LAS100977 0.625 μg | Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1) | 0.205 Liters | Standard Error 0.039 |
| LAS100977 1.25 μg | Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1) | 0.278 Liters | Standard Error 0.039 |
| LAS100977 2.5 μg | Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1) | 0.346 Liters | Standard Error 0.039 |
| Salbutamol 400 μg | Change From Baseline to Trough Forced Expiratory Volume in One Second (FEV1) | -0.076 Liters | Standard Error 0.039 |
Secondary
Change From Baseline to Trough Forced Vital Capacity (FVC)
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). Trough at Day 2 was computed as the average of the two values measured at 23 and 24 hours after administration of the morning dose of investigational medicinal product on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time frame: Baseline and +23 h +24 h post-dose
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Trough Forced Vital Capacity (FVC) | -0.028 Liters | Standard Error 0.035 |
| LAS100977 0.313 μg | Change From Baseline to Trough Forced Vital Capacity (FVC) | 0.094 Liters | Standard Error 0.035 |
| LAS100977 0.625 μg | Change From Baseline to Trough Forced Vital Capacity (FVC) | 0.050 Liters | Standard Error 0.035 |
| LAS100977 1.25 μg | Change From Baseline to Trough Forced Vital Capacity (FVC) | 0.111 Liters | Standard Error 0.035 |
| LAS100977 2.5 μg | Change From Baseline to Trough Forced Vital Capacity (FVC) | 0.120 Liters | Standard Error 0.035 |
| Salbutamol 400 μg | Change From Baseline to Trough Forced Vital Capacity (FVC) | -0.065 Liters | Standard Error 0.035 |
Secondary
Peak Forced Expiratory Volume in One Second (FEV1)
The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning on Day 1. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.
Time frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Population: ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak Forced Expiratory Volume in One Second (FEV1) | 2.855 Liters | Standard Error 0.045 |
| LAS100977 0.313 μg | Peak Forced Expiratory Volume in One Second (FEV1) | 3.129 Liters | Standard Error 0.045 |
| LAS100977 0.625 μg | Peak Forced Expiratory Volume in One Second (FEV1) | 3.177 Liters | Standard Error 0.045 |
| LAS100977 1.25 μg | Peak Forced Expiratory Volume in One Second (FEV1) | 3.225 Liters | Standard Error 0.045 |
| LAS100977 2.5 μg | Peak Forced Expiratory Volume in One Second (FEV1) | 3.260 Liters | Standard Error 0.045 |
| Salbutamol 400 μg | Peak Forced Expiratory Volume in One Second (FEV1) | 3.207 Liters | Standard Error 0.045 |
Secondary
Peak Forced Vital Capacity (FVC)
The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h
Population: ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Peak Forced Vital Capacity (FVC) | 4.483 Liters | Standard Error 0.034 |
| LAS100977 0.313 μg | Peak Forced Vital Capacity (FVC) | 4.578 Liters | Standard Error 0.034 |
| LAS100977 0.625 μg | Peak Forced Vital Capacity (FVC) | 4.590 Liters | Standard Error 0.034 |
| LAS100977 1.25 μg | Peak Forced Vital Capacity (FVC) | 4.622 Liters | Standard Error 0.034 |
| LAS100977 2.5 μg | Peak Forced Vital Capacity (FVC) | 4.641 Liters | Standard Error 0.034 |
| Salbutamol 400 μg | Peak Forced Vital Capacity (FVC) | 4.622 Liters | Standard Error 0.034 |
Secondary
Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected. The number of participants analyzed differed between timepoints - the number of participants analyzed at 0.25 h is shown.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h, +6 h, +8 h, +12 h, +14 h, +23 h, +24 h, and +36 h
Population: Patients in the ITT population with available data at the timepoints of interest. ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 2.407 Percent change | Standard Error 1.356 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 1.519 Percent change | Standard Error 1.09 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | -0.611 Percent change | Standard Error 1.473 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | -1.903 Percent change | Standard Error 1.559 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 2.682 Percent change | Standard Error 1.439 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | -2.117 Percent change | Standard Error 1.464 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 0.402 Percent change | Standard Error 1.627 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 2.752 Percent change | Standard Error 1.505 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 1.904 Percent change | Standard Error 1.574 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 4.435 Percent change | Standard Error 1.479 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 4.288 Percent change | Standard Error 1.596 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 2.449 Percent change | Standard Error 1.205 |
| Placebo | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 3.520 Percent change | Standard Error 1.434 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 14.118 Percent change | Standard Error 1.482 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 14.741 Percent change | Standard Error 1.427 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 15.965 Percent change | Standard Error 1.472 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 5.451 Percent change | Standard Error 1.444 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 10.847 Percent change | Standard Error 1.614 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 13.661 Percent change | Standard Error 1.424 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 7.084 Percent change | Standard Error 1.453 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 9.427 Percent change | Standard Error 1.551 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 13.452 Percent change | Standard Error 1.35 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 6.396 Percent change | Standard Error 1.554 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 8.325 Percent change | Standard Error 1.084 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 15.400 Percent change | Standard Error 1.589 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 11.757 Percent change | Standard Error 1.199 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 8.918 Percent change | Standard Error 1.461 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 15.128 Percent change | Standard Error 1.482 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 16.371 Percent change | Standard Error 1.428 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 8.846 Percent change | Standard Error 1.084 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 12.388 Percent change | Standard Error 1.614 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 17.960 Percent change | Standard Error 1.59 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 17.190 Percent change | Standard Error 1.472 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 6.955 Percent change | Standard Error 1.445 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 14.307 Percent change | Standard Error 1.35 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 12.006 Percent change | Standard Error 1.199 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 5.589 Percent change | Standard Error 1.555 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 11.008 Percent change | Standard Error 1.544 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 16.490 Percent change | Standard Error 1.425 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 18.199 Percent change | Standard Error 1.482 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 14.251 Percent change | Standard Error 1.614 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 11.771 Percent change | Standard Error 1.544 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 9.893 Percent change | Standard Error 1.445 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 10.975 Percent change | Standard Error 1.461 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 8.742 Percent change | Standard Error 1.555 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 10.789 Percent change | Standard Error 1.084 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 14.362 Percent change | Standard Error 1.199 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 16.927 Percent change | Standard Error 1.35 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 18.509 Percent change | Standard Error 1.428 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 20.357 Percent change | Standard Error 1.477 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 19.454 Percent change | Standard Error 1.59 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 19.080 Percent change | Standard Error 1.425 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 17.170 Percent change | Standard Error 1.616 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 20.550 Percent change | Standard Error 1.47 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 16.715 Percent change | Standard Error 1.196 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 13.511 Percent change | Standard Error 1.081 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 16.716 Percent change | Standard Error 1.555 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 21.155 Percent change | Standard Error 1.587 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 10.370 Percent change | Standard Error 1.558 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 20.612 Percent change | Standard Error 1.421 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | 13.716 Percent change | Standard Error 1.458 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 19.733 Percent change | Standard Error 1.478 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | 12.375 Percent change | Standard Error 1.449 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 20.226 Percent change | Standard Error 1.43 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 18.336 Percent change | Standard Error 1.352 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 24 hr | -1.736 Percent change | Standard Error 1.482 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 2 hr | 17.755 Percent change | Standard Error 1.438 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 3 hr | 14.537 Percent change | Standard Error 1.484 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 23 hr | -3.649 Percent change | Standard Error 1.464 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.25 hr | 17.744 Percent change | Standard Error 1.098 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 8 hr | 4.493 Percent change | Standard Error 1.497 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 14 hr | 1.892 Percent change | Standard Error 1.594 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 0.5 hr | 18.806 Percent change | Standard Error 12.209 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 36 hr | 2.098 Percent change | Standard Error 1.572 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 1 hr | 19.085 Percent change | Standard Error 1.36 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 12 hr | 0.997 Percent change | Standard Error 1.639 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 4 hr | 10.608 Percent change | Standard Error 1.6 |
| Salbutamol 400 μg | Percentage Change From Baseline in Forced Expiratory Volume (FEV1) at Each Timepoint | 6 hr | 5.796 Percent change | Standard Error 1.438 |
Secondary
Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1)
Baseline was the average of the two values measured just prior to the administration of the dose of investigational medicinal product at Day 1 of each visit (time points -45 min and -15 min). The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.
Time frame: Baseline and +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Population: ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 7.555 Percent change | Standard Error 1.655 |
| LAS100977 0.313 μg | Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 18.282 Percent change | Standard Error 1.651 |
| LAS100977 0.625 μg | Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 20.212 Percent change | Standard Error 1.651 |
| LAS100977 1.25 μg | Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 21.809 Percent change | Standard Error 1.651 |
| LAS100977 2.5 μg | Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 23.077 Percent change | Standard Error 1.65 |
| Salbutamol 400 μg | Percentage Change From Baseline in Peak Forced Expiratory Volume in One Second (FEV1) | 21.374 Percent change | Standard Error 1.658 |
Secondary
Time to Peak Forced Expiratory Volume in One Second (FEV1)
The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 were selected.
Time frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h post-dose
Population: ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Peak Forced Expiratory Volume in One Second (FEV1) | 2.3 Hours | Standard Deviation 1.3 |
| LAS100977 0.313 μg | Time to Peak Forced Expiratory Volume in One Second (FEV1) | 2.6 Hours | Standard Deviation 1.3 |
| LAS100977 0.625 μg | Time to Peak Forced Expiratory Volume in One Second (FEV1) | 3.0 Hours | Standard Deviation 1.1 |
| LAS100977 1.25 μg | Time to Peak Forced Expiratory Volume in One Second (FEV1) | 3.1 Hours | Standard Deviation 0.9 |
| LAS100977 2.5 μg | Time to Peak Forced Expiratory Volume in One Second (FEV1) | 3.0 Hours | Standard Deviation 1.1 |
| Salbutamol 400 μg | Time to Peak Forced Expiratory Volume in One Second (FEV1) | 1.1 Hours | Standard Deviation 0.8 |
Secondary
Time to Peak Forced Vital Capacity (FVC)
The peak was computed as the highest value observed for each patient during the 4-hour period immediately after the investigational medicinal product administered in the morning. At each time point, three technically adequate lung function measurements were performed by spirometry according to the acceptability and repeatability criteria of the ATS/ERS; the highest values for the FEV1 and FVC were selected.
Time frame: +15 min, +30 min, +1 h, +2 h, +3 h, +4 h
Population: ITT population defined as patients who took at least one dose of investigational medicinal product and had at least a baseline and one post-dose value of FEV1 from at least one treatment period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to Peak Forced Vital Capacity (FVC) | 2.1 Hours | Standard Deviation 1.4 |
| LAS100977 0.313 μg | Time to Peak Forced Vital Capacity (FVC) | 1.8 Hours | Standard Deviation 1.4 |
| LAS100977 0.625 μg | Time to Peak Forced Vital Capacity (FVC) | 2.3 Hours | Standard Deviation 1.4 |
| LAS100977 1.25 μg | Time to Peak Forced Vital Capacity (FVC) | 2.1 Hours | Standard Deviation 1.2 |
| LAS100977 2.5 μg | Time to Peak Forced Vital Capacity (FVC) | 2.2 Hours | Standard Deviation 1.4 |
| Salbutamol 400 μg | Time to Peak Forced Vital Capacity (FVC) | 1.5 Hours | Standard Deviation 1.2 |