A Study to Assess the Efficacy of Budesonide/Albuterol Metered-dose Inhaler (BDA MDI/PT027) on Exercise-induced Bronchoconstriction in Adults and Adolescents With Asthma

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, randomized, double-blind, single-dose, placebo-controlled, 2-period, crossover study to evaluate the efficacy and safety of budesonide/albuterol metered-dose inhaler (BDA MDI/PT027) as compared with a placebo metered-dose inhaler (placebo MDI) on exercise-induced bronchoconstriction (EIB) in adult and adolescent subjects with asthma. Subjects will receive each study treatment on separate visits and undergo a treadmill exercise challenge test for up to 10 minutes so that the effect of study treatment on exercise-induced bronchoconstriction can be evaluated.

Official Title
-----------------
A Randomized, Double-blind, Single-dose, 2-Period, Crossover Study to Assess the Efficacy of PT027 Compared With Placebo on Exercise-Induced Bronchoconstriction in Adult and Adolescent Subjects With Asthma

Conditions
-----------------
Exercise Induced Bronchospasm

Intervention / Treatment
-----------------
* Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg
* Combination Product: Placebo metered-dose inhaler


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female or male aged 12 to 70 years at the time of informed consent Documented history of asthma for at least 6 months prior to Visit 1 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/rapid-acting β 2-adrenoreceptor agonist (SABA) used as needed Low- to medium-dose maintenance therapy with inhaled corticosteroid (ICS) and SABA used as needed Demonstrate acceptable MDI administration technique (use of a spacer device during the treatment phase is not permitted) Exclusion Criteria: Chronic obstructive pulmonary disease or other significant lung disease (eg, chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, or bronchopulmonary dysplasia), including regular or occasional use of oxygen Systemic corticosteroids (SCS) use (any dose and any indication) within 3 months before Visit 1 History of life-threatening asthma, defined by past intubations for asthma, or intensive care unit admission for asthma within the prior 24 months 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 Unable to tolerate the lung function testing performed after exercise challenge test without use of rescue medication 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) Completed treatment for lower respiratory infection within 6 weeks prior to Visit 1, regardless if resulting in accompanying asthma symptoms aggravation or not Upper respiratory infection involving antibiotic treatment not resolved within 7 days prior to Visit 1 Received any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab) or investigational biologic within 3 months before Visit 1, or any other prohibited medication Current treatment with any investigational product or within the last 30 days of Visit 1. Historical or current evidence of a clinically significant disease Cancer not in complete remission for at least 5 years before Visit 1 Hospitalization for psychiatric disorder or attempted suicide within 1 year of Visit 1 History of psychiatric disease or intellectual deficiency Having a scheduled or planned hospitalization during the study Inability (and/or unwillingness) to abstain from protocol-defined prohibited medications during the study. 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. Significant abuse of alcohol or drugs

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A/B - Treatment with BDA MDI 160/180 followed by treatment with Placebo MDI<br>Subjects randomized to receive a single dose of BDA MDI 160/180 in treatment period 1, and a single dose of Placebo MDI in treatment period 2. | Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg<br>* Budesonide/albuterol sulfate combination inhalation aerosol single dose<br>* Other names: BDA MDI 160/180 μg (PT027);Combination Product: Placebo metered-dose inhaler<br>* Placebo inhalation aerosol single dose<br>* Other names: Placebo MDI;|
| Experimental: B/A - Treatment with Placebo MDI followed by treatment with BDA MDI 160/180<br>Subjects randomized to receive a single dose of Placebo MDI in treatment period 1, and a single dose of BDA MDI 160/180 in treatment period 2. | Combination Product: Budesonide/albuterol sulfate metered-dose inhaler 160/180 μg<br>* Budesonide/albuterol sulfate combination inhalation aerosol single dose<br>* Other names: BDA MDI 160/180 μg (PT027);Combination Product: Placebo metered-dose inhaler<br>* Placebo inhalation aerosol single dose<br>* Other names: Placebo MDI;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 60 minutes post exercise challenge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With a Maximum Percentage Fall in FEV₁ Post-exercise Challenge of <10% | 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% was determined. | Up to 60 minutes post exercise challenge |