Asthma, Exercise-Induced
Conditions
Keywords
Asthma, Exercise-Induced Allergies, Bronchial Spasm, Albuterol, Budesonide, Bronchodilator Agents, Anti-Inflammatory Agents
Brief summary
The purpose of this Phase III, multicentre, randomized, double-blind, single-dose, 2-period, crossover study is to assess the efficacy and safety of PT027 (budesonide/albuterol sulfate) metered-dose inhaler compared with placebo on exercise-induced bronchoconstriction in adult patients with asthma. Subjects will receive each study treatment on separate visits and undergo a treadmill exercise challenge test so that the effect of study treatment on exercise-induced bronchoconstriction can be evaluated
Interventions
DRUGBudesonide/albuterol metered-dose inhaler 160/180 μg
Budesonide/albuterol combination aerosol for inhalation, single dose (given as 2 actuations of 80/90 μg)
Placebo aerosol for inhalation, single dose (given as 2 actuations)
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Female or male aged 18 to 70 years at the time of informed consent. 2. Documented history of asthma for at least 6 months prior to Visit 1 3. Receiving 1 of the following asthma therapies with stable dosing for at least the 4 weeks before Visit 1 (no other asthma therapies are permitted during the study): * Short-acting β 2-adrenoreceptor agonist (SABA) used as needed; * Low- to medium-dose maintenance therapy with inhaled corticosteroid (ICS) and SABA used as needed. 4. Demonstrate acceptable MDI administration technique (use of a spacer device during the treatment phase is not permitted)
Exclusion criteria
1. Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, bronchopulmonary dysplasia), including regular or occasional use of oxygen. 2. Systemic corticosteroids (SCS) use (any dose and any indication) within 3 months before Visit 1. 3. History of life-threatening asthma, defined by past intubations for asthma, or intensive care unit admission for asthma within the prior 24 months. 4. Receiving regular maintenance treatment with prohibited anti-inflammatory or long-acting bronchodilator asthma medication (inhaled, nebulized, oral, or systemic) within 1 month prior to Visit 1. 5. Unable to tolerate the lung function testing performed after exercise challenge test without use of rescue medication. 6. Current smokers, former smokers with \>10 pack-years history, or former smokers who stopped smoking \<6 months before Visit 1 (including all forms of tobacco, e-cigarettes \[vaping\], and marijuana). 7. Completed treatment for lower respiratory infection within 6 weeks prior to Visit 1, regardless if resulting in accompanying asthma symptoms aggravation or not. 8. Upper respiratory infection involving antibiotic treatment not resolved within 7 days prior to Visit 1. 9. Received any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab) or investigational biologic within 3 months before Visit 1, or any other prohibited medication. 10. Historical or current evidence of a clinically significant disease. 11. History of psychiatric disease or intellectual deficiency. 12. Having a scheduled or planned hospitalization during the study. 13. Inability (and/or unwillingness) to abstain from protocol-defined prohibited medications during the study. 14. Use of any herbal products by inhalation or nebulizer within 2 weeks of Visit 1 and/or the unwillingness to stop during the study duration. 15. Significant abuse of alcohol or drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | Up to 60 minutes post-exercise challenge | Lung function was measured by spirometry. Spirometry assessments were completed 5 minutes before dosing, 30 minutes after dosing (baseline; 5 minutes before the exercise challenge), and then 5, 10, 15, 30, and 60 minutes after the exercise challenge. A reduction in FEV₁ was expected due to the effects of asthma and exercise on breathing and lung function. The percentage fall in FEV₁ was calculated based on the baseline value and maximum percentage fall value during the 60-minute assessment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% and <20% | Up to 60 minutes post exercise challenge | The percentage fall in FEV₁ was calculated based on the baseline value and maximum percentage fall value during the 60-minute assessment period, and the percentage of subjects with a maximum percentage fall \<10% and \<20% was determined |
| Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | Up to 60 minutes post exercise challenge | The percentage fall in FEV₁ at each time point was calculated based on the baseline value and percentage fall value during the 60-minute assessment period at each time point. |
| Post-Exercise FEV1 Area Under the Curve From 0 to 30 Minutes (AUC0-30min) | Up to 30 minutes post exercise challenge | FEV1 AUC0-30min will be derived for the changes from the post-dose, pre-exercise baseline using the trapezoidal rule and will be normalized by dividing by the actual time (in minutes) from dosing to the last included measurement, scheduled at 30 minutes post-exercise challenge. |
| Time To Recovery | Up to 60 minutes post exercise challenge | Time to recovery will be derived as the time (minutes) post-exercise challenge in which the FEV1 result returns to within 10% of the value recorded at the post-dose, pre-exercise baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Through study completion, an average of 4 weeks | The safety profile will be evaluated using vital signs, physical examination, electrocardiograms (ECGs) and AE data. |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Budesonide/Albuterol Metered-dose Inhaler (BDA MDI) 160/180 - Placebo Participants administered BDA MDI 160/180 during 1st period and placebo in 2nd period | 31 |
| Placebo - Budesonide/Albuterol Metered-dose Inhaler (BDA MDI) 160/180 Participants administered placebo during 1st period and BDA MDI 160/180 in 2nd period | 33 |
| Total | 64 |
Baseline characteristics
| Characteristic | Budesonide/Albuterol Metered-dose Inhaler (BDA MDI) 160/180 - Placebo | Placebo - Budesonide/Albuterol Metered-dose Inhaler (BDA MDI) 160/180 | Total |
|---|---|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 14.5 | 43.2 years STANDARD_DEVIATION 13.9 | 41.1 years STANDARD_DEVIATION 14.2 |
| Age, Customized < 65 years | 30 Participants | 32 Participants | 62 Participants |
| Age, Customized >= 65 years | 1 Participants | 1 Participants | 2 Participants |
| Pre-dose pre-exercise challenge test (ECT) forced expiratory volume in 1 second (FEV1) | 2.925 liters STANDARD_DEVIATION 0.826 | 3.042 liters STANDARD_DEVIATION 0.877 | 2.985 liters STANDARD_DEVIATION 0.848 |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 31 Participants | 32 Participants | 63 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 31 Participants | 33 Participants | 64 Participants |
| Sex: Female, Male Female | 19 Participants | 17 Participants | 36 Participants |
| Sex: Female, Male Male | 12 Participants | 16 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 64 | 0 / 64 |
| other Total, other adverse events | 1 / 64 | 2 / 64 |
| serious Total, serious adverse events | 0 / 64 | 0 / 64 |
Outcome results
Primary
Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge
Lung function was measured by spirometry. Spirometry assessments were completed 5 minutes before dosing, 30 minutes after dosing (baseline; 5 minutes before the exercise challenge), and then 5, 10, 15, 30, and 60 minutes after the exercise challenge. A reduction in FEV₁ was expected due to the effects of asthma and exercise on breathing and lung function. The percentage fall in FEV₁ was calculated based on the baseline value and maximum percentage fall value during the 60-minute assessment period.
Time frame: Up to 60 minutes post-exercise challenge
Population: Full analysis set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| BDA MDI 160/180 | Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | All subjects | 6.95 Percent fall |
| BDA MDI 160/180 | Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | Non-ICS | 6.28 Percent fall |
| BDA MDI 160/180 | Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | ICS | 7.29 Percent fall |
| Placebo | Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | All subjects | 24.46 Percent fall |
| Placebo | Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | Non-ICS | 26.62 Percent fall |
| Placebo | Maximum Percentage Fall From Post-dose, Pre-exercise Baseline in Forced Expiratory Volume in 1 Second (FEV₁) Observed up to 60 Minutes Post-exercise Challenge | ICS | 23.28 Percent fall |
p-value: <0.00195% CI: [-19.78, -15.25]Mixed Models Analysis
Secondary
Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge
The percentage fall in FEV₁ at each time point was calculated based on the baseline value and percentage fall value during the 60-minute assessment period at each time point.
Time frame: Up to 60 minutes post exercise challenge
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| BDA MDI 160/180 | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 10 min Post-ECT | 3.16 Percent |
| BDA MDI 160/180 | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 30 min Post-ECT | 2.64 Percent |
| BDA MDI 160/180 | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 15 min Post-ECT | 4.20 Percent |
| BDA MDI 160/180 | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 60 min Post-ECT | 0.56 Percent |
| BDA MDI 160/180 | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 5 min Post-ECT | 1.68 Percent |
| Placebo | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 60 min Post-ECT | 3.10 Percent |
| Placebo | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 5 min Post-ECT | 9.79 Percent |
| Placebo | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 10 min Post-ECT | 17.98 Percent |
| Placebo | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 15 min Post-ECT | 19.14 Percent |
| Placebo | Percentage Fall From Post-dose, Pre-exercise Baseline in FEV1 at Each Time Point Within 60 Minutes Post-exercise Challenge | 30 min Post-ECT | 11.85 Percent |
Secondary
Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% and <20%
The percentage fall in FEV₁ was calculated based on the baseline value and maximum percentage fall value during the 60-minute assessment period, and the percentage of subjects with a maximum percentage fall \<10% and \<20% was determined
Time frame: Up to 60 minutes post exercise challenge
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BDA MDI 160/180 | Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% and <20% | Maximum percentage fall <10% | 48 Participants |
| BDA MDI 160/180 | Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% and <20% | Maximum percentage fall <20% | 62 Participants |
| Placebo | Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% and <20% | Maximum percentage fall <10% | 2 Participants |
| Placebo | Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% and <20% | Maximum percentage fall <20% | 14 Participants |
Secondary
Post-Exercise FEV1 Area Under the Curve From 0 to 30 Minutes (AUC0-30min)
FEV1 AUC0-30min will be derived for the changes from the post-dose, pre-exercise baseline using the trapezoidal rule and will be normalized by dividing by the actual time (in minutes) from dosing to the last included measurement, scheduled at 30 minutes post-exercise challenge.
Time frame: Up to 30 minutes post exercise challenge
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BDA MDI 160/180 | Post-Exercise FEV1 Area Under the Curve From 0 to 30 Minutes (AUC0-30min) | -0.10 liter | Standard Deviation 0.16 |
| Placebo | Post-Exercise FEV1 Area Under the Curve From 0 to 30 Minutes (AUC0-30min) | -0.44 liter | Standard Deviation 0.23 |
Secondary
Time To Recovery
Time to recovery will be derived as the time (minutes) post-exercise challenge in which the FEV1 result returns to within 10% of the value recorded at the post-dose, pre-exercise baseline.
Time frame: Up to 60 minutes post exercise challenge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BDA MDI 160/180 | Time To Recovery | 56 Participants |
| Placebo | Time To Recovery | 6 Participants |
Other Pre-specified
Number of Participants With Adverse Events (AEs)
The safety profile will be evaluated using vital signs, physical examination, electrocardiograms (ECGs) and AE data.
Time frame: Through study completion, an average of 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BDA MDI 160/180 | Number of Participants With Adverse Events (AEs) | 1 Participants |
| Placebo | Number of Participants With Adverse Events (AEs) | 2 Participants |