Pharmacodynamic Bioequivalence of Metered Dose Inhalers of Albuterol Sulfate in Patients With Stable Mild Asthma

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the pharmacodynamic bioequivalence of the test product to the reference product, using bronchoprovocation (methacholine challenge testing) in adult patients with stable mild asthma.

Detailed Description
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A Multicenter, Double-Blind, Double-Dummy, Placebo-Controlled, 5-Treatment, Randomized, Crossover Study to Demonstrate the Pharmacodynamic Bioequivalence of Test and Reference Metered Dose Inhalers containing Albuterol Sulfate using Bronchoprovocation in Adult Patients with Stable Mild Asthma

Official Title
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Comparison of the Pharmacodynamic Profile of Test and Reference Metered Dose Inhalers (MDIs) Containing Albuterol Sulfate Using Bronchoprovocation in Adult Patients With Stable Mild Asthma

Conditions
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Mild Persistent Asthma

Intervention / Treatment
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* Other: methacholine chloride
* Drug: placebo ProAir HFA
* Drug: ProAir HFA
* Drug: Lupin albuterol HFA MDI
* Drug: placebo Lupin albuterol HFA MDI


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. Forced Expiratory Volume in 1 second ( FEV1) ≥ 80% of predicted. Airway responsiveness to methacholine demonstrated by a pre-albuterol dose (baseline) PC20 ≤ 8 mg/ml. Nonsmokers for at least 1 year 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: Conditions which could alter airway reactivity to methacholine (e.g., pneumonia, upper respiratory tract infection, lower respiratory tract, viral bronchitis and/or sinobronchitis) within six weeks preceding the screening visit. History of seasonal asthma exacerbations, in which case the patient 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, or chronic condition that could put the safety of the patient at risk during the study or affect the efficacy and safety analyses during the study. Treatment in an emergency room, urgent care center, or hospitalization for acute asthmatic symptoms within the past 6 months or need for daily oral corticosteroids within past 3 months. Known intolerance or hypersensitivity to any component of the albuterol metered dose inhaler (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 dose<br>Placebo dose: 1 actuation each from 2 different placebo ProAir HFA inhalation aerosols and one actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols | Other: methacholine chloride<br> <br> Drug: placebo ProAir HFA<br> <br> Drug: placebo Lupin albuterol HFA MDI<br> <br> |
| Active Comparator: 90 mcg ProAir HFA<br>90 mcg of ProAir HFA: 1 actuation each from ProAir HFA inhalation aerosol and the placebo ProAir HFA inhalation aerosol and 1 actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols | Other: methacholine chloride<br> <br> Drug: placebo ProAir HFA<br> <br> Drug: ProAir HFA<br> <br> Drug: placebo Lupin albuterol HFA MDI<br> <br> |
| Active Comparator: 180 mcg ProAir HFA<br>180 mcg of ProAir HFA: 1 actuation each from 2 different ProAir HFA inhalation aerosols and 1 actuation each from 2 different placebo Lupin albuterol HFA MDI inhalation aerosols | Other: methacholine chloride<br> <br> Drug: ProAir HFA<br> <br> Drug: placebo Lupin albuterol HFA MDI<br> <br> |
| Experimental: 90 mcg Lupin albuterol HFA MDI<br>90 mcg of Lupin albuterol HFA MDI product: 1 actuation each from the Lupin albuterol HFA MDI inhalation aerosol and the placebo Lupin albuterol HFA MDI inhalation aerosol and 1 actuation each from 2 different placebo ProAir HFA inhalation aerosols | Other: methacholine chloride<br> <br> Drug: placebo ProAir HFA<br> <br> Drug: Lupin albuterol HFA MDI<br> <br> Drug: placebo Lupin albuterol HFA MDI<br> <br> |
| Experimental: 180 mcg Lupin albuterol HFA MDI<br>180 mcg of Lupin albuterol HFA MDI: 1 actuation each from 2 different Lupin albuterol HFA MDI inhalation aerosols and 1 actuation each from 2 different placebo ProAir HFA product inhalation aerosols | Other: methacholine chloride<br> <br> Drug: placebo ProAir HFA<br> <br> Drug: Lupin albuterol HFA MDI<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-dose PC20 Concentration After Receiving Differing Doses of Test, Reference, or Placebo | The primary efficacy endpoint was the postdose PC20 following administration of differing doses of albuterol (or placebo) by inhalation. The 20% reduction in FEV1 was determined relative to the saline stage FEV1 measured before albuterol or placebo administration. Additionally, an analysis of superiority to placebo was performed for the T and R products prior to the BE determination. In this study the ITT and PP populations were identical. | Post-dose at Visits 2-6 of the study, a total of approximately 4 weeks. |