Assessment of the Safety, Efficacy, PK, and Extrapulmonary Pharmacodynamics (PD) of Albuterol Sulfate Pressurized Inhalation Suspension (Hereafter Referred to as AS MDI) Compared to Proventil as an Active Control in Subjects With Asthma

Study Overview
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Brief Summary
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This is a randomized, cumulative dose, open-label, 2-period crossover, multi-center study to assess the safety, efficacy, PK, and extrapulmonary PD of cumulative doses of AS MDI compared to cumulative doses of Proventil as an active control in subjects with mild to moderate asthma

Detailed Description
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This is a randomized, cumulative dose, open-label, 2-period crossover, multi-center study to assess the safety, efficacy, PK, and extrapulmonary pharmacodynamics (PD) of cumulative doses of Albuterol Sulfate Pressurized Inhalation Suspension (hereafter referred to as AS MDI) compared to cumulative doses of Proventil® hydrofluoroalkane (HFA; hereafter referred to as Proventil) as an active control in subjects with mild to moderate asthma.

Official Title
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A Randomized, Cumulative Dose, Open-label, 2-period Crossover, Multi-center Study to Assess the Safety, Efficacy, PK, and Extrapulmonary Pharmacodynamics (PD) of Cumulative Doses of Albuterol Sulfate Pressurized Inhalation Suspension (Hereafter Referred to as AS MDI) Compared to Cumulative Doses of Proventil® Hydrofluoroalkane (HFA; Hereafter Referred to as Proventil) as an Active Control in Subjects With Mild to Moderate Asthma (ASPEN)

Conditions
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Asthma

Intervention / Treatment
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* Drug: AS MDI
* Drug: Proventil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have stable (for 6 months) physician-diagnosed asthma with historical documentation of the diagnosis Must be receiving 1 of the following required inhaled asthma therapies listed below for at least the last 30 days; Only SABA, which is used as needed for rescue, or Low to medium doses of ICS (alone or in combination with LABA), used regularly as maintenance asthma therapy Demonstrate acceptable spirometry performance (ie, meet American Thoracic Society [ATS]/European Respiratory Society [ERS] acceptability/repeatability criteria Pre-bronchodilator FEV1 of ≥50 to <80% predicted normal value after withholding SABA ≥6 hours Confirmed FEV1 reversibility to Ventolin, defined as a post-Ventolin increase in FEV1 of ≥15% Only 2 reversibility testing attempts are allowed 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) Oral corticosteroid use (any dose) within 6 weeks Received any marketed (eg, omalizumab, mepolizumab, reslizumab) or investigational biologic within 3 months or 5 half-lives, whichever is longer, or any other medication specifically prohibited by the protocol Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months (including all forms of tobacco, e-cigarettes [vaping], and marijuana) Life-threatening asthma as defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s) Historical or current evidence of a clinically significant disease Cancer not in complete remission for at least 5 years Hospitalized for psychiatric disorder or attempted suicide within 1 year Unable to abstain from protocol-defined prohibited medications during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AS MDI<br>AS MDI 1+1+2+4+8 inhalations of 90 μg per inhalation | Drug: AS MDI<br>* AS MDI 1+1+2+4+8 inhalations of 90 μg per inhalation<br>|
| Active Comparator: Proventil<br>Proventil 1+1+2+4+8 inhalations of 90 μg per inhalation | Drug: Proventil<br>* Proventil 1+1+2+4+8 inhalations of 90 μg per inhalation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline-adjusted FEV1 30 Minutes After Each Cumulative Dose | Forced expiratory volume in 1 second (FEV1) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation | At the two study treatment visits, FEV1 (forced expiratory volume in 1 second) will be measured prior to drug administration and 5 times, once at 30 minutes after each of the 5 doses | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline-adjusted FEV1 AUC0-6 After the Last Cumulative Dose | The baseline-adjusted FEV1 AUC0-6 is the area under the curve for change from baseline calculated using the trapezoidal rule and normalized by dividing the AUC by the length of follow up post the last cumulative dose (typically 6 hours) (spirometry will be obtained at 5, 15, 30, 45, 60, 120, 180, and 240 minutes post-dose) normalized for length of follow up). | Over 6 hours post dose on Day 1 |