Bronchoprovocation Study to Evaluate the Pharmacodynamics of Albuterol Sulfate Inhalation Aerosol, eq 90 mcg Base

Study Overview
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Brief Summary
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This randomized, single-dose, double-blind, double-dummy, four-period, four-sequence, four-treatment, placebo and active controlled, comparative, multiple-center, crossover-design bronchoprovocation study has been designed to evaluate the pharmacodynamic equivalence of albuterol sulfate HFA inhalation aerosol, eq 90 mcg base (Amneal Ireland Limited) to PROAIR® HFA (albuterol sulfate) Inhalation Aerosol, eq 90 mcg base (Teva Respiratory, LLC) in patients with stable mild asthma.

Official Title
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A Randomized, Single-Dose, Double-Blind, Double-Dummy, Four-Period, Four-Sequence, Four-Treatment, Placebo and Active Controlled, Comparative, Multiple-Center, Crossover-Design, Bronchoprovocation Study to Evaluate the Pharmacodynamic Equivalence of Albuterol Sulfate Inhalation Aerosol, eq 90 mcg Base (Amneal Ireland Limited) to PROAIR® HFA (Albuterol Sulfate) Inhalation Aerosol, eq 90 mcg Base (Teva Respiratory, LLC) in Patients With Stable, Mild Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Placebo
* Drug: 90 mcg Reference Product
* Drug: 180 mcg Reference Product
* Drug: 90 mcg Test Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non-pregnant female subjects (18-65 years of age). Stable mild asthmatics based on National Asthma Education and Prevention Program (NAEPP) guidelines. FEV1 ≥ 80% of predicted. Airway responsiveness to methacholine demonstrated by a pre-albuterol-dose (baseline) PC20 ≤ 8 mg/mL. Nonsmokers for at least six months prior to the study and a maximum smoking history of five pack-years (the equivalent of one pack per day for five years). Written informed consent Exclusion Criteria: Evidence of upper or lower respiratory tract infection (e.g., pneumonia, bronchitis, sinusitis) within six weeks prior to the study. History of seasonal asthma exacerbations, in which case the subject should be studied outside of the relevant allergen season. History of cystic fibrosis, bronchiectasis or other respiratory diseases. History of cardiovascular, renal, neurologic, liver or endocrine dysfunction, including ECG with evidence of ischemic heart disease. Treatment in an emergency room or hospitalization for acute asthmatic symptoms or need for daily oral corticosteroids within past three months. Known intolerance or hypersensitivity to any component of the albuterol MDI.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Product<br>One actuation each from two different placebo Reference inhalation aerosols and one actuation each from two different placebo Test inhalation aerosols | Drug: Placebo<br>* Placebo Product<br>|
| Active Comparator: 90 mcg Reference Product<br>One actuation each from the Reference inhalation aerosol and the placebo Reference inhalation aerosol and one actuation each from two different placebo Test inhalation aerosols | Drug: 90 mcg Reference Product<br>* 90 mcg Reference Product - PROAIR HFA ALBUTEROL SULFATE [TEVA RESPIRATORY, LLC]<br>* Other names: Albuterol;|
| Active Comparator: 180 mcg Reference Product<br>One actuation each from two different Reference inhalation aerosol and one actuation each from two different placebo Test inhalation aerosols | Drug: 180 mcg Reference Product<br>* 180 mcg Reference Product- PROAIR HFA ALBUTEROL SULFATE [TEVA RESPIRATORY, LLC]<br>* Other names: Albuterol;|
| Experimental: 90 mcg Test Product<br>One actuation each from the Test inhalation aerosol and the placebo Test inhalation aerosol and one actuation each from two different placebo Reference inhalation aerosols | Drug: 90 mcg Test Product<br>* 90 mcg Test Product - ALBUTEROL SULFATE HFA [AMNEAL IRELAND LIMITED]<br>* Other names: Albuterol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Pharmacodynamic Endpoint Post-dose PC20 | Provocative concentration of the methacholine challenge agent required to reduce the FEV1 by 20% following administration of differing doses of albuterol or placebo by inhalation. The 20% reduction in FEV1 will be determined relative to the post-saline FEV1 measure before the placebo or albuterol administration. | 6 weeks |