Asthma
Conditions
Keywords
Asthma, dry powder inhaler, short-acting beta2-agonist, SABA, bronchoconstriction, bronchodilation, bronchodilator, metered dose inhaler
Brief summary
The study will measure the change in lung function in subjects with asthma after inhaling from either of two inhalers: Albuterol Spiromax® or placebo.
Interventions
DRUGPlacebo MDPI
Placebo MDPI administered as 2 inhalations 4 times a day (QID) (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 12 weeks.
DRUGAlbuterol MDPI
Albuterol MDPI administered as 2 inhalations 4 times a day (QID) (at approximately 7:00 AM, 12 noon, 5:00 PM, and bedtime) for 12 weeks.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written informed consent/assent * General good health * Persistent asthma, with an FEV1 50-80% predicted. * Ability to perform spirometry in an acceptable manner as per protocol guidelines. * Ability to perform PEFR with a handheld peak flow meter. * Demonstration of reversible bronchoconstriction as verified by a 15% or greater increase from baseline FEV1. * Taking inhaled corticosteroids at a stable dose for at least 4 weeks prior to the Screening Visit. * Non-smokers. * Capable of understanding the requirements, risks, and benefits of study participation. * Other inclusion criteria apply.
Exclusion criteria
* Participation in any investigational drug trial within the 30 days preceding the Screening Visit (SV). * A known hypersensitivity to albuterol or any of the excipients in the formulations. * History of severe milk protein allergy. * History of a respiratory infection or disorder that has not resolved within the 2 weeks preceding the Screening Visit (SV). * Currently requires treatment with β2-adrenergic receptor antagonists or non-selective β-receptor blocking agents. * History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation. * Any asthma exacerbation requiring oral corticosteroids within 3 months of the Screening Visit (SV). A subject must not have had any hospitalization for asthma within 6 months prior to the Screening Visit (SV). * Historical or current evidence of any clinically significant non-asthmatic acute or chronic condition including. * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period | Day 1, Day 8 and Day 85 | FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) of FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8 | Day 8 | FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 8. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min. |
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85 | Day 85 | FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 85. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min. |
| Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1 | Day 1 | FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 1. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min. |
| Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Day 1 (Baseline), Day 85 | Physical exam was recorded as normal or abnormal based on physician assessment. Format for results is: Test Baseline/Endpoint HEENT = head, eyes, ears, nose, throat |
| Participants With Clinically Significant Vital Sign Assessments | Day 8, Day 85 | For both standard and serial vital signs, participants were seated for at least 5 minutes before vital signs were assessed. Heart rate was obtained prior to the blood pressure measurement. Serial heart rate and blood pressure were conducted in the sitting position prior to the spirometry assessment; baseline measures were taken pre-dose at -30 ± 5 and -5 minutes on Day 1. Day 85 serial vital sign measures were taken in the sitting position prior to spirometry assessments pre-dose at -30 ± 5 and -5 minutes, then post-dose at 30 (±5) minutes, 1hr (± 10 min), 2hr (± 10 min), 3hr (± 10 min), 4hr (± 10 min), 5hr (± 10 min) and 6 hr (± 10 min). Serial heart rate and blood pressure measurements that were elevated to the following criteria were considered clinically significant: Systolic blood pressure: \> 160 beats/minute Diastolic blood pressure: \>100 beats/minute Heart rate: \>120 beats/minute |
| Participants With Adverse Events | Day 1 to Day 92 | Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Effect (Change in FEV1 of 12% From Baseline Within 30 Minutes Postdose) | Day 1, Day 8, Day 85 | — |
| Duration of Response Measured From the Time Post-dosing to the First Time After the Response Onset (Increase ≥12% Above Baseline) When the FEV1 Decreases to Less Than 12% Above Baseline (Within 6 Hours After Dosing) for Those Who Responded in 30 Minutes | Day 1, Day 8, Day 85 | — |
| Time to Onset of Effect (Change in FEV1 of 15% From Baseline Within 30 Minutes Postdose)for Those Who Responded in 30 Minutes | Day 1, Day 8, Day 85 | — |
| Percent Change From Baseline in FEV1 AUC 0-6 Over the 12-week Treatment Period | Day 1, Day 8, Day 85 | — |
| Percent of Symptom Free Days on the Patient Diary | Treatment days 1 through 85 | — |
| Percent of Rescue Medication Free Days in the Patient Diary | Treatment days 1 through 85 | — |
| Morning Peak Expiratory Flow Reading Reported on Patient Diary | Treatment days 1 through 85 | — |
| Duration of Response on Days 1, 8 and 85 | Day 1, Day 8, Day 85 | Duration of response measured from the time post-dosing to the first time after the response onset (increase ≥15% above baseline) when the FEV1 decreases to less than 15% above baseline (within 6 hours after dosing) for those who responded within 30 minutes |
| Percent Change From Baseline in FEV1 AUC 0-6 | Day 1 | — |
| Percent Change From Baseline in FEV1 AUC | Day 8 | — |
| Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose Over the 12-week Treatment Period | Day 1, Day 8, Day 85 | — |
| Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 1 | Day 1 | — |
| Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 8 | Day 8 | — |
| Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 85 | Day 85 | — |
Countries
United States
Participant flow
Pre-assignment details
384 patients screened; 180 patients were excluded on the basis of inclusion criteria, 4 due to exclusion criteria, 21 patients withdrew consent, 1 patient was lost to follow-up before the baseline visit, 6 patients had other reasons, and 14 patients failed to meet randomization criteria at the end of the run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Placebo MDPI Placebo multi-dose dry powder inhaler (MDPI) administered as 2 inhalations four times a day for 12 weeks. | 79 |
| Albuterol MDPI Albuterol multi-dose dry powder inhaler (MDPI) at a dose of 720 micrograms per day administered as 2 inhalations of 90 mcg /inhalation four times a day for 12 weeks. | 79 |
| Total | 158 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo MDPI | Albuterol MDPI | Total |
|---|---|---|---|
| Age, Continuous | 40.3 years STANDARD_DEVIATION 16.84 | 37.3 years STANDARD_DEVIATION 16.89 | 38.8 years STANDARD_DEVIATION 16.88 |
| Age, Customized 12-17 years | 14 participants | 16 participants | 30 participants |
| Age, Customized 18-64 years | 63 participants | 60 participants | 123 participants |
| Age, Customized 65+ years | 2 participants | 3 participants | 5 participants |
| Body Mass Index | 28.6 kg/m^2 STANDARD_DEVIATION 6.92 | 29.2 kg/m^2 STANDARD_DEVIATION 8.22 | 28.9 kg/m^2 STANDARD_DEVIATION 7.58 |
| Height | 169.5 cm STANDARD_DEVIATION 9.47 | 168.9 cm STANDARD_DEVIATION 9.27 | 169.2 cm STANDARD_DEVIATION 9.35 |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Black | 18 participants | 21 participants | 39 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 participants | 6 participants | 9 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 76 participants | 73 participants | 149 participants |
| Race/Ethnicity, Customized Other | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Pacific Islander | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 59 participants | 55 participants | 114 participants |
| Sex: Female, Male Female | 47 Participants | 44 Participants | 91 Participants |
| Sex: Female, Male Male | 32 Participants | 35 Participants | 67 Participants |
| Weight | 82.4 kg STANDARD_DEVIATION 21.34 | 83.4 kg STANDARD_DEVIATION 24.2 | 82.9 kg STANDARD_DEVIATION 22.75 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 78 | 9 / 79 |
| serious Total, serious adverse events | 0 / 78 | 0 / 79 |
Outcome results
Primary
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. It represents the weighted average (by the trapezoidal rule) of FEV1 AUC 0-6 measures adjusted for the baseline measure (i.e., change from baseline at each timepoint) recorded on days 1, 8 and 85 of the treatment period. The baseline for each study day was the average of the 2 pre-dose FEV1 measurements on that study day. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
Time frame: Day 1, Day 8 and Day 85
Population: Full analysis set which includes all participants in the intent-to-treat (ITT) population who received at least 1 dose of study medication and had at least 1 post-baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo MDPI | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period | 0.28 L*hr | Standard Error 0.091 |
| Albuterol MDPI | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) Over the 12-week Treatment Period | 1.11 L*hr | Standard Error 0.092 |
p-value: <0.000195% CI: [0.57, 1.08]mixed-model repeated-measures (MMRM)
Secondary
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 1. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
Time frame: Day 1
Population: Full analysis set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo MDPI | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1 | 0.52 L*hr |
| Albuterol MDPI | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 1 | 1.58 L*hr |
p-value: <0.000195% CI: [0.68, 1.46]mixed model repeated measures (MMRM)
Secondary
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 8. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
Time frame: Day 8
Population: Full analysis set of participants with data at the time point
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo MDPI | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8 | 0.26 L*hr |
| Albuterol MDPI | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 8 | 0.99 L*hr |
p-value: <0.000195% CI: [0.41, 1.06]mixed model repeated measures (MMRM)
Secondary
Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85
FEV1 AUC 0-6 is the area under the effect-time curve from time 0 (pre-dose) up to 6 hours post-dose. The baseline was the average of the 2 pre-dose FEV1 measurements on that study day. The baseline-adjustment refers to change from baseline at each post dose timepoint recorded on Day 85. FEV1 was measured using spirometry. Spirometry assessments were obtained predose at -30 ± 5, and - 5 minutes, then post dose at 5 ± 2, 15 ± 5, 30 ± 5, 45 ± 5 minutes, and at 1hr ± 5 min, 2hr ± 5 min, 3hr ± 5 min, 4hr ± 5 min, 5hr ± 5 min, and 6hr ± 5 min.
Time frame: Day 85
Population: Full analysis set of participants with data at the time point
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo MDPI | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85 | 0.06 L*hr |
| Albuterol MDPI | Baseline-adjusted Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC 0-6) on Day 85 | 0.74 L*hr |
p-value: <0.000195% CI: [0.38, 0.99]mixed model repeated measures (MMRM)
Secondary
Participants With Adverse Events
Adverse events (AEs) summarized in this table are those that began or worsened after treatment with study drug (treatment-emergent AEs). An adverse event was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
Time frame: Day 1 to Day 92
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo MDPI | Participants With Adverse Events | Any adverse event | 25 participants |
| Placebo MDPI | Participants With Adverse Events | Severe adverse events | 1 participants |
| Placebo MDPI | Participants With Adverse Events | Treatment-related AE | 1 participants |
| Placebo MDPI | Participants With Adverse Events | Deaths | 0 participants |
| Placebo MDPI | Participants With Adverse Events | Other serious AEs | 0 participants |
| Placebo MDPI | Participants With Adverse Events | Withdrawn from study due to AEs | 0 participants |
| Albuterol MDPI | Participants With Adverse Events | Other serious AEs | 0 participants |
| Albuterol MDPI | Participants With Adverse Events | Any adverse event | 22 participants |
| Albuterol MDPI | Participants With Adverse Events | Deaths | 0 participants |
| Albuterol MDPI | Participants With Adverse Events | Withdrawn from study due to AEs | 0 participants |
| Albuterol MDPI | Participants With Adverse Events | Treatment-related AE | 1 participants |
| Albuterol MDPI | Participants With Adverse Events | Severe adverse events | 1 participants |
Secondary
Participants With Clinically Significant Vital Sign Assessments
For both standard and serial vital signs, participants were seated for at least 5 minutes before vital signs were assessed. Heart rate was obtained prior to the blood pressure measurement. Serial heart rate and blood pressure were conducted in the sitting position prior to the spirometry assessment; baseline measures were taken pre-dose at -30 ± 5 and -5 minutes on Day 1. Day 85 serial vital sign measures were taken in the sitting position prior to spirometry assessments pre-dose at -30 ± 5 and -5 minutes, then post-dose at 30 (±5) minutes, 1hr (± 10 min), 2hr (± 10 min), 3hr (± 10 min), 4hr (± 10 min), 5hr (± 10 min) and 6 hr (± 10 min). Serial heart rate and blood pressure measurements that were elevated to the following criteria were considered clinically significant: Systolic blood pressure: \> 160 beats/minute Diastolic blood pressure: \>100 beats/minute Heart rate: \>120 beats/minute
Time frame: Day 8, Day 85
Population: Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo MDPI | Participants With Clinically Significant Vital Sign Assessments | Systolic blood pressure - high | 3 participants |
| Placebo MDPI | Participants With Clinically Significant Vital Sign Assessments | Diastolic blood pressure - high | 3 participants |
| Placebo MDPI | Participants With Clinically Significant Vital Sign Assessments | Heart rate - high | 0 participants |
| Albuterol MDPI | Participants With Clinically Significant Vital Sign Assessments | Systolic blood pressure - high | 0 participants |
| Albuterol MDPI | Participants With Clinically Significant Vital Sign Assessments | Diastolic blood pressure - high | 1 participants |
| Albuterol MDPI | Participants With Clinically Significant Vital Sign Assessments | Heart rate - high | 1 participants |
Secondary
Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group
Physical exam was recorded as normal or abnormal based on physician assessment. Format for results is: Test Baseline/Endpoint HEENT = head, eyes, ears, nose, throat
Time frame: Day 1 (Baseline), Day 85
Population: Safety population. Only participants with both baseline and endpoint physical examination findings are summarized. Two placebo participants were missing endpoint physical examinations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Lymph nodes Abnormal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | HEENT Normal/Abnormal | 12 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | HEENT Abnormal/Normal | 11 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | HEENT Abnormal/Abnormal | 8 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Chest and Lungs Normal/Normal | 66 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Chest and Lungs Normal/Abnormal | 8 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Chest and Lungs Abnormal/Normal | 2 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Chest and Lungs Abnormal/abnormal | 1 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Heart Normal/Normal | 76 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Heart Normal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Heart Abnormal/Normal | 1 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Heart Abnormal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Abdomen Normal/Normal | 75 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Abdomen Normal/Abnormal | 1 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Abdomen Abnormal/Normal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Abdomen Abnormal/Abnormal | 1 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Musculoskeletal Normal/Normal | 74 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Musculoskeletal Normal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Musculoskeletal Abnormal/Normal | 3 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Musculoskeletal Abnormal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Skin Normal/Normal | 75 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Skin Normal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Skin Abnormal/Normal | 2 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Skin Abnormal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Lymph nodes Normal/Normal | 77 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Lymph nodes Normal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Lymph nodes Abnormal/Normal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Neurological Normal/Normal | 76 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Neurological Normal/Abnormal | 1 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Neurological Abnormal/Normal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Neurological Abnormal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | General appearance Normal/Normal | 76 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | General appearance Normal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | General appearance Abnormal/Normal | 1 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | General appearance Abnormal/Abnormal | 0 participants |
| Placebo MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | HEENT Normal/Normal | 46 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Musculoskeletal Abnormal/Normal | 1 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | General appearance Normal/Normal | 76 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | HEENT Normal/Abnormal | 5 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Musculoskeletal Abnormal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | HEENT Abnormal/Normal | 12 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Neurological Normal/Normal | 78 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | HEENT Abnormal/Abnormal | 11 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Skin Normal/Normal | 73 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Chest and Lungs Normal/Normal | 67 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | HEENT Normal/Normal | 50 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Chest and Lungs Normal/Abnormal | 4 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Skin Normal/Abnormal | 1 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Chest and Lungs Abnormal/Normal | 7 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Neurological Normal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Chest and Lungs Abnormal/abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Skin Abnormal/Normal | 4 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Heart Normal/Normal | 77 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | General appearance Normal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Heart Normal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Skin Abnormal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Heart Abnormal/Normal | 1 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Neurological Abnormal/Normal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Heart Abnormal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Lymph nodes Normal/Normal | 78 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Abdomen Normal/Normal | 77 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | General appearance Abnormal/Abnormal | 1 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Abdomen Normal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Lymph nodes Normal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Abdomen Abnormal/Normal | 1 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | General appearance Abnormal/Normal | 1 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Abdomen Abnormal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Lymph nodes Abnormal/Normal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Musculoskeletal Normal/Normal | 76 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Neurological Abnormal/Abnormal | 0 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Musculoskeletal Normal/Abnormal | 1 participants |
| Albuterol MDPI | Physical Examination Findings Shifts From Baseline to Endpoint by Treatment Group | Lymph nodes Abnormal/Abnormal | 0 participants |
Other Pre-specified
Duration of Response Measured From the Time Post-dosing to the First Time After the Response Onset (Increase ≥12% Above Baseline) When the FEV1 Decreases to Less Than 12% Above Baseline (Within 6 Hours After Dosing) for Those Who Responded in 30 Minutes
Time frame: Day 1, Day 8, Day 85
Other Pre-specified
Duration of Response on Days 1, 8 and 85
Duration of response measured from the time post-dosing to the first time after the response onset (increase ≥15% above baseline) when the FEV1 decreases to less than 15% above baseline (within 6 hours after dosing) for those who responded within 30 minutes
Time frame: Day 1, Day 8, Day 85
Other Pre-specified
Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 1
Time frame: Day 1
Other Pre-specified
Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 8
Time frame: Day 8
Other Pre-specified
Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose on Day 85
Time frame: Day 85
Other Pre-specified
Maximum Percent Change From Baseline in FEV1 Within 2 Hours Post Dose Over the 12-week Treatment Period
Time frame: Day 1, Day 8, Day 85
Other Pre-specified
Morning Peak Expiratory Flow Reading Reported on Patient Diary
Time frame: Treatment days 1 through 85
Other Pre-specified
Percent Change From Baseline in FEV1 AUC
Time frame: Day 8
Other Pre-specified
Percent Change From Baseline in FEV1 AUC
Time frame: Day 85
Other Pre-specified
Percent Change From Baseline in FEV1 AUC 0-6
Time frame: Day 1
Other Pre-specified
Percent Change From Baseline in FEV1 AUC 0-6 Over the 12-week Treatment Period
Time frame: Day 1, Day 8, Day 85
Other Pre-specified
Percent of Rescue Medication Free Days in the Patient Diary
Time frame: Treatment days 1 through 85
Other Pre-specified
Percent of Symptom Free Days on the Patient Diary
Time frame: Treatment days 1 through 85
Other Pre-specified
Time to Onset of Effect (Change in FEV1 of 12% From Baseline Within 30 Minutes Postdose)
Time frame: Day 1, Day 8, Day 85
Other Pre-specified
Time to Onset of Effect (Change in FEV1 of 15% From Baseline Within 30 Minutes Postdose)for Those Who Responded in 30 Minutes
Time frame: Day 1, Day 8, Day 85