Asthma
Conditions
Keywords
Albuterol Spiromax, ProAir HFA, albuterol sulfate
Brief summary
This is a multicenter, randomized, double-blind, double-dummy, placebo-controlled, single-dose, 5-treatment, 5-period, 5-way crossover study in pediatric patients with persistent asthma. The primary purpose of this study is to compare the efficacy and safety of Albuterol Spiromax with that of ProAir HFA in pediatric asthma patients at 2 delivered dose levels equivalent to 90 mcg and 180 mcg of albuterol base.
Detailed description
The study consists of a screening visit (SV) followed by up to 16 days by a treatment period comprising 5 visits (TV1-TV5). The treatment period visits will each be separated by a washout period lasting 2-7 days. During each treatment period visit, the forced expiratory volume in 1 second (FEV1) will be determined at 30 minutes and again immediately prior to the commencement of study medication administration, and 5, 15, 30, 45, 60, 120, 180, 240, 300, and 360 minutes after completion of study medication administration.
Interventions
Albuterol Spiromax® Inhalation Aerosol contains 90 mcg albuterol per actuation orally inhaled in a single dose dry powder inhaler (DPI). Participants took doses at either the 90 or 180 mcg levels. If the higher level, two DPIs filled with Albuterol Spiromax® were used.
DRUGProAir HFA
ProAir® HFA Inhalation Aerosol contains 90 mcg albuterol per actuation orally inhaled in a single dose metered dose inhaler (MDI). Participants took doses at either the 90 or 180 mcg levels. If the higher level, two MDIs filled with ProAir HFA were used.
DRUGPlacebo
Single dose MDIs and DPIs containing placebo taken as a single orally-inhaled actuation each.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
4 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent/assent signed and dated by the patient and/or parent/caregiver/legal guardian (as appropriate) before conducting any study related procedure 2. Male or pre-menarchal female 4-11 years of age, inclusive, as of the screening visit 3. Has a documented physician diagnosis of persistent asthma of a minimum of 6 months duration that has been stable for at least 4 weeks prior to the screening visit. The asthma diagnosis must be in accordance with the National Asthma Education and Prevention Program Guidelines Expert Panel Report 3 (EPR3) 4. Has the ability to self-perform spirometry reproducibly per American Thoracic Society (ATS) guidelines 5. Has forced expiratory volume in 1 second (FEV1) 60-90% predicted for age, height, and gender at the screening visit based on the pediatric population standards as per protocol. Notes: (1) Predicted values of 59.50-59.99% may be rounded up to 60% and 90.01-90.49% rounded down to 90%. (2) Patients who at the screening visit fail to meet the predicted spirometry values for study entry may be allowed a single attempt to re-qualify on another day, but they must re-qualify no later than 16 days following the first attempt. 6. Demonstrates reversible bronchoconstriction as verified by a 15% or greater increase in baseline FEV1 within 30 minutes following inhalation of 180 mcg of albuterol to 200 mcg of fluticasone propionate per day or equivalent), leukotriene modifiers (LTM), inhaled cromones, or on β2-agonists alone as needed. The Inhaled corticosteroid (ICS), LTM, and cromone doses must have been stable for at least 4 weeks prior to the screening visit and are expected to be maintained for the duration of the study 7. Is maintained on low-dose inhaled corticosteroids (\[ICS\], less than or equal to 200 mcg of fluticasone propionate per day or equivalent), leukotriene modifiers (LTM), inhaled cromones, or on β2-agonists alone as needed. The ICS, LTM, and cromone doses must have been stable for at least 4 weeks prior to the screening visit and are expected to be maintained for the duration of the study 8. Can self-perform peak expiratory flow rate (PEF) measurements with a handheld peak flow meter 9. Has the ability to demonstrate acceptable and reproducible inhalation technique with the Spiromax and metered dose inhaler (MDI) devices * Other inclusion criteria apply.
Exclusion criteria
1. Known hypersensitivity to albuterol or any of the excipients in the inhaler formulations (lactose, ethanol, etc.) 2. Participation (receiving study medication) in any investigational drug trial within the 30 days preceding the screening visit or planned participation in another investigational drug trial at any time during this trial 3. History of severe milk protein allergy 4. History of a respiratory infection or disorder (including, but not limited to bronchitis, pneumonia, acute or chronic sinusitis, otitis media, influenza, etc.) that has not resolved within 4 weeks preceding the screening visit 5. Any asthma exacerbation requiring oral corticosteroids within 3 months of the screening visit. A patient must not have had any hospitalization for asthma within 6 months prior to the screening visit. 6. History of life-threatening asthma that is defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest, or hypoxic seizures 7. Use of any prohibited concomitant medications within the washout period prescribed per protocol prior to the screening visit. 8. Use of any medication for asthma or allergic rhinitis that is prohibited per the protocol 9. The dosage of any required intranasal corticosteroid and/or cromone has not been stable for at least 2 weeks prior to the screening visit. 10. Treated with oral or injectable corticosteroids within the 6 weeks before the screening visit. 11. Initiation of immunotherapy during the study period or dose escalation during the study period. Patients being treated with immunotherapy prior to the screening visit must be using a stable (maintenance) dose (90 days or more) to be considered for inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose | Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administrati | Percent predicted FEV1: measured FEV1 as a percent of the predicted values for the patients of similar characteristics. Predicted FEV1 values were computed and adjusted for age, height, and gender for patients aged 4-5 years (Eigen et al 2001) and for patients aged 6-11 years (Quanjer et al 1995) using ATS/European Thoracic Society (ERS) criteria applicable to pediatric patients (ATS/ERS 2007). The percent predicted FEV1 (PPFEV1) area under the curve (AUC)0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose PPFEV1 values from each post-dose PPFEV1 determination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6) | Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administrati | FEV1 AUC0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose FEV1 values from each post-dose FEV1 determination. |
| Participants With Treatment-Emergent Adverse Events | Day 1 up to Day 35 | 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 as mild (no limitation of usual activities), moderate, or severe (inability to carry out usual 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. |
Countries
United States
Participant flow
Recruitment details
Of the 102 patients screened, 61 patients at 14 centers in the US met entry criteria and were considered to be eligible for enrollment into the study. 41 patients were not enrolled: 33 were excluded due to inclusion criteria, 1 patient withdrew consent, 3 patients were lost to follow-up before the baseline visit, and 4 patients for other reasons.
Pre-assignment details
Participants were randomized in a 1:1:1:1:1:1:1:1:1:1 fashion into 10 treatment sequences with 6 participants in 9 of the sequences and 7 participants in the remaining sequence.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants were assigned to 1 of 10 possible treatment sequences for five treatments, separated by 2-7 days. Treatments were single inhalations of Albuterol MDPI 90 mcg, Albuterol MDPI 180 mcg, ProAir HFA MDI 90 mcg, ProAir HFA MDI 180 mcg, and placebo. | 61 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Treatment Period 2 | Other | 1 |
| Treatment Period 3 | Other | 2 |
| Treatment Period 5 | Other | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 9.0 years STANDARD_DEVIATION 1.6 |
| Body Mass Index | 19.5 kg/m^2 STANDARD_DEVIATION 4.35 |
| Duration of Asthma 10 to <15 years | 8 participants |
| Duration of Asthma 1 to <5 years | 22 participants |
| Duration of Asthma <3 months | 0 participants |
| Duration of Asthma 3 to <6 months | 0 participants |
| Duration of Asthma 5 to <10 years | 30 participants |
| Duration of Asthma 6 months to <1 year | 1 participants |
| Duration of Asthma None | 0 participants |
| Duration of Previous Dry-Powder Inhaler (DPI) Experience 10 to <15 years | 0 participants |
| Duration of Previous Dry-Powder Inhaler (DPI) Experience 1 to <5 years | 9 participants |
| Duration of Previous Dry-Powder Inhaler (DPI) Experience <3 months | 2 participants |
| Duration of Previous Dry-Powder Inhaler (DPI) Experience 3 to <6 months | 1 participants |
| Duration of Previous Dry-Powder Inhaler (DPI) Experience 5 to <10 years | 0 participants |
| Duration of Previous Dry-Powder Inhaler (DPI) Experience 6 months to <1 year | 3 participants |
| Duration of Previous Dry-Powder Inhaler (DPI) Experience None | 46 participants |
| Duration of Previous Metered-Dose Inhaler (MDI) Experience 10 to <15 years | 3 participants |
| Duration of Previous Metered-Dose Inhaler (MDI) Experience 1 to <5 years | 34 participants |
| Duration of Previous Metered-Dose Inhaler (MDI) Experience <3 months | 1 participants |
| Duration of Previous Metered-Dose Inhaler (MDI) Experience 3 to <6 months | 0 participants |
| Duration of Previous Metered-Dose Inhaler (MDI) Experience 5 to <10 years | 19 participants |
| Duration of Previous Metered-Dose Inhaler (MDI) Experience 6 months to <1 year | 3 participants |
| Duration of Previous Metered-Dose Inhaler (MDI) Experience None | 1 participants |
| Height | 138.7 cm STANDARD_DEVIATION 10.2 |
| Race/Ethnicity, Customized Black | 29 participants |
| Race/Ethnicity, Customized Other | 4 participants |
| Race/Ethnicity, Customized White | 28 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 38 Participants |
| Weight | 38.2 kg STANDARD_DEVIATION 12.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 61 | 0 / 61 | 3 / 61 | 0 / 61 | 0 / 61 |
| serious Total, serious adverse events | 0 / 61 | 0 / 61 | 0 / 61 | 0 / 61 | 0 / 61 |
Outcome results
Primary
Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose
Percent predicted FEV1: measured FEV1 as a percent of the predicted values for the patients of similar characteristics. Predicted FEV1 values were computed and adjusted for age, height, and gender for patients aged 4-5 years (Eigen et al 2001) and for patients aged 6-11 years (Quanjer et al 1995) using ATS/European Thoracic Society (ERS) criteria applicable to pediatric patients (ATS/ERS 2007). The percent predicted FEV1 (PPFEV1) area under the curve (AUC)0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose PPFEV1 values from each post-dose PPFEV1 determination.
Time frame: Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administrati
Population: Full analysis set (FAS) included all participants in the ITT population who received at least 1 dose of study medication, had a baseline assessment, and had at least 1 post baseline assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol Spiromax 90 mcg | Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose | 46.6 %predicted FEV1*hour | Standard Error 6.27 |
| Albuterol Spiromax 180 mcg | Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose | 48.0 %predicted FEV1*hour | Standard Error 6.24 |
| ProAir HFA 90 mcg | Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose | 37.9 %predicted FEV1*hour | Standard Error 6.25 |
| ProAir HFA 180 mcg | Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose | 49.1 %predicted FEV1*hour | Standard Error 6.26 |
| Placebo | Baseline-Adjusted Area-Under-The-Percent-Predicted Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose | 25.4 %predicted FEV1*hour | Standard Error 6.25 |
Comparison: The mean difference between each active group and placebo was tested in a sequential manner:~* Albuterol MDPI 180 mcg to placebo~* Albuterol MDPI 90 mcg to placebo~* ProAir HFA 180 mcg to placebo~* ProAir HFA 90 mcg to placebo Each test was 2 sided and done at the 0.05 level of significance. However, if a test was not significant at this level, no further tests were done. This sequential process assured that the overall alpha level for the entire series was not greater than 0.05.p-value: <0.000195% CI: [13, 32.2]ANOVA
Comparison: The mean difference between each active group and placebo was tested in a sequential manner:~* Albuterol MDPI 180 mcg to placebo~* Albuterol MDPI 90 mcg to placebo~* ProAir HFA 180 mcg to placebo~* ProAir HFA 90 mcg to placebo Each test was 2 sided and done at the 0.05 level of significance. However, if a test was not significant at this level, no further tests were done. This sequential process assured that the overall alpha level for the entire series was not greater than 0.05.p-value: <0.000195% CI: [11.6, 30.81]ANOVA
Comparison: The mean difference between each active group and placebo was tested in a sequential manner:~* Albuterol MDPI 180 mcg to placebo~* Albuterol MDPI 90 mcg to placebo~* ProAir HFA 180 mcg to placebo~* ProAir HFA 90 mcg to placebo Each test was 2 sided and done at the 0.05 level of significance. However, if a test was not significant at this level, no further tests were done. This sequential process assured that the overall alpha level for the entire series was not greater than 0.05.p-value: <0.000195% CI: [14.13, 33.23]ANOVA
Comparison: The mean difference between each active group and placebo was tested in a sequential manner:~* Albuterol MDPI 180 mcg to placebo~* Albuterol MDPI 90 mcg to placebo~* ProAir HFA 180 mcg to placebo~* ProAir HFA 90 mcg to placebo Each test was 2 sided and done at the 0.05 level of significance. However, if a test was not significant at this level, no further tests were done. This sequential process assured that the overall alpha level for the entire series was not greater than 0.05.p-value: 0.010795% CI: [2.93, 22.05]ANOVA
Comparison: Pre-specified, exploratory analysisp-value: 0.777295% CI: [-11, 8.23]ANOVA
Comparison: Pre-specified, exploratory analysisp-value: 0.022695% CI: [-20.8, -1.59]ANOVA
Secondary
Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6)
FEV1 AUC0-6 was calculated using the linear trapezoidal rule, and baseline adjustment was made by subtracting the average of the 2 pre-dose FEV1 values from each post-dose FEV1 determination.
Time frame: Treatment visits 1-5 (approximately days 1, 6, 11, 16, and 21); -35 and -5 minutes prior to dosing and 5 (±2), 15 (±5), 30 (±5), 45 (±5), 60 (±5), 120 (±5), 180 (±5), 240 (±5), 300 (±5), and 360 (±5) minutes after the completion of study drug administrati
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Albuterol Spiromax 90 mcg | Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6) | 0.88 L*hour | Standard Error 0.14 |
| Albuterol Spiromax 180 mcg | Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6) | 0.93 L*hour | Standard Error 0.14 |
| ProAir HFA 90 mcg | Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6) | 0.74 L*hour | Standard Error 0.14 |
| ProAir HFA 180 mcg | Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6) | 0.93 L*hour | Standard Error 0.14 |
| Placebo | Baseline-Adjusted Area-Under-The- Forced Expiratory Volume In 1 Second (FEV1) Versus Time Curve Over 6 Hours Post-Dose (FEV1 AUC0-6) | 0.48 L*hour | Standard Error 0.14 |
Comparison: The mean difference between each active group and placebo was tested in a sequential manner:~* Albuterol MDPI 180 mcg to placebo~* Albuterol MDPI 90 mcg to placebo~* ProAir HFA 180 mcg to placebo~* ProAir HFA 90 mcg to placebo Each test was 2 sided and done at the 0.05 level of significance. However, if a test was not significant at this level, no further tests were done. This sequential process assured that the overall alpha level for the entire series was not greater than 0.05.p-value: <0.000195% CI: [0.26, 0.64]ANOVA
Comparison: The mean difference between each active group and placebo was tested in a sequential manner:~* Albuterol MDPI 180 mcg to placebo~* Albuterol MDPI 90 mcg to placebo~* ProAir HFA 180 mcg to placebo~* ProAir HFA 90 mcg to placebo Each test was 2 sided and done at the 0.05 level of significance. However, if a test was not significant at this level, no further tests were done. This sequential process assured that the overall alpha level for the entire series was not greater than 0.05.p-value: <0.000195% CI: [0.21, 0.59]ANOVA
Comparison: The mean difference between each active group and placebo was tested in a sequential manner:~* Albuterol MDPI 180 mcg to placebo~* Albuterol MDPI 90 mcg to placebo~* ProAir HFA 180 mcg to placebo~* ProAir HFA 90 mcg to placebo Each test was 2 sided and done at the 0.05 level of significance. However, if a test was not significant at this level, no further tests were done. This sequential process assured that the overall alpha level for the entire series was not greater than 0.05.p-value: <0.000195% CI: [0.26, 0.64]ANOVA
Comparison: The mean difference between each active group and placebo was tested in a sequential manner:~* Albuterol MDPI 180 mcg to placebo~* Albuterol MDPI 90 mcg to placebo~* ProAir HFA 180 mcg to placebo~* ProAir HFA 90 mcg to placebo Each test was 2 sided and done at the 0.05 level of significance. However, if a test was not significant at this level, no further tests were done. This sequential process assured that the overall alpha level for the entire series was not greater than 0.05.p-value: 0.006295% CI: [0.08, 0.45]ANOVA
Comparison: Pre-specified, exploratory analysisp-value: 0.634295% CI: [-0.23, 0.14]ANOVA
Comparison: Pre-specified, exploratory analysisp-value: 0.048895% CI: [-0.38, 0]ANOVA
Secondary
Participants With Treatment-Emergent 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 as mild (no limitation of usual activities), moderate, or severe (inability to carry out usual 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 up to Day 35
Population: The safety population included all randomized patients who received at least 1 dose of randomized study medication. In this population, treatment was assigned based upon the treatment patients actually receive regardless of the treatment to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albuterol Spiromax 90 mcg | Participants With Treatment-Emergent Adverse Events | TEAE leading to withdrawal | 0 participants |
| Albuterol Spiromax 90 mcg | Participants With Treatment-Emergent Adverse Events | Treatment-related AE | 0 participants |
| Albuterol Spiromax 90 mcg | Participants With Treatment-Emergent Adverse Events | Serious AE | 0 participants |
| Albuterol Spiromax 90 mcg | Participants With Treatment-Emergent Adverse Events | Severe TEAE | 0 participants |
| Albuterol Spiromax 90 mcg | Participants With Treatment-Emergent Adverse Events | Death | 0 participants |
| Albuterol Spiromax 90 mcg | Participants With Treatment-Emergent Adverse Events | Related TEAE | 0 participants |
| Albuterol Spiromax 180 mcg | Participants With Treatment-Emergent Adverse Events | Treatment-related AE | 2 participants |
| Albuterol Spiromax 180 mcg | Participants With Treatment-Emergent Adverse Events | Severe TEAE | 0 participants |
| Albuterol Spiromax 180 mcg | Participants With Treatment-Emergent Adverse Events | TEAE leading to withdrawal | 0 participants |
| Albuterol Spiromax 180 mcg | Participants With Treatment-Emergent Adverse Events | Death | 0 participants |
| Albuterol Spiromax 180 mcg | Participants With Treatment-Emergent Adverse Events | Related TEAE | 0 participants |
| Albuterol Spiromax 180 mcg | Participants With Treatment-Emergent Adverse Events | Serious AE | 0 participants |
| ProAir HFA 90 mcg | Participants With Treatment-Emergent Adverse Events | Related TEAE | 0 participants |
| ProAir HFA 90 mcg | Participants With Treatment-Emergent Adverse Events | Severe TEAE | 0 participants |
| ProAir HFA 90 mcg | Participants With Treatment-Emergent Adverse Events | Treatment-related AE | 5 participants |
| ProAir HFA 90 mcg | Participants With Treatment-Emergent Adverse Events | Death | 0 participants |
| ProAir HFA 90 mcg | Participants With Treatment-Emergent Adverse Events | Serious AE | 0 participants |
| ProAir HFA 90 mcg | Participants With Treatment-Emergent Adverse Events | TEAE leading to withdrawal | 0 participants |
| ProAir HFA 180 mcg | Participants With Treatment-Emergent Adverse Events | Serious AE | 0 participants |
| ProAir HFA 180 mcg | Participants With Treatment-Emergent Adverse Events | Treatment-related AE | 1 participants |
| ProAir HFA 180 mcg | Participants With Treatment-Emergent Adverse Events | Death | 0 participants |
| ProAir HFA 180 mcg | Participants With Treatment-Emergent Adverse Events | Related TEAE | 0 participants |
| ProAir HFA 180 mcg | Participants With Treatment-Emergent Adverse Events | Severe TEAE | 0 participants |
| ProAir HFA 180 mcg | Participants With Treatment-Emergent Adverse Events | TEAE leading to withdrawal | 0 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Treatment-related AE | 1 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Death | 0 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Severe TEAE | 0 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | TEAE leading to withdrawal | 0 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Serious AE | 0 participants |
| Placebo | Participants With Treatment-Emergent Adverse Events | Related TEAE | 0 participants |