A Randomized, Single-dose, Double-blind, Double-dummy, Placebo and Active Controlled, Crossover Design Study Using Bronchoprovocation to Evaluate the Pharmacodynamic Equivalence of the Test and Reference Metered Dose Inhalers (MDIs) Containing Albuterol Sulfate in Adult Patients with Stable Mild Asthma
Overview
- Phase
- Not Applicable
- Intervention
- Albuterol Sulfate inhalation Placebo
- Conditions
- Mild Asthma
- Sponsor
- Intech Biopharm Ltd.
- Enrollment
- 148
- Locations
- 12
- Primary Endpoint
- Post-dose PC20 Concentration
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The objective of this study is to evaluate the pharmacodynamic (PD) bioequivalence (BE) of albuterol inhalers, test formulation: Albuterol Sulfate HFA inhalation aerosol 108 mcg (equal to albuterol base 90 mcg) per actuation and reference formulation: ProAir HFA (albuterol sulfate) or FDA authorized generic: Albuterol Sulfate HFA (Teva Pharmaceutical USA, Inc.) Inhalation Aerosol 108 mcg (equal to albuterol base 90 mcg) per actuation manufactured by two different manufacturers using methacholine bronchoprovocation challenge test in patients with stable mild asthma.
Detailed Description
This study will be conducted using the single-dose, randomized, double-blind, double-dummy, four-sequence, four-treatment, and multiple-center study design to evaluate the PD bioequivalence between the test albuterol sulfate (T) inhalation aerosol 108 mcg per actuation (eq. to albuterol base 90 mcg/puff) and the reference albuterol sulfate (R) (ProAir HFA or FDA authorized generic: Albuterol Sulfate HFA \[Teva Pharmaceutical USA, Inc.\]) inhalation aerosol 108 mcg per actuation (equal to albuterol base 90 mcg/puff). The two products will be studied using a crossover design in patients with stable mild asthma by administering a minimum of 3 doses of reference product (0, 90, 180 mcg albuterol) and 2 doses of test product (0, 90 mcg albuterol). The bronchodilation potency of albuterol sulfate are measured by the inhibition effects of methacholine challenge on the bronchodilation, as indicated by increase in the provocative concentration of methacholine required to produce a 20% decrease in FEV1 (PC20).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male, non-pregnant and non-lactating female subjects (20-65 years of age, inclusive).
- •A clinical diagnosis of mild asthma with historical documentation of the asthma diagnosis according to either: (1) the National Asthma Education and Prevention Program (NAEPP) guidelines (2007) or (2) the Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention (2020).
- •Stable mild asthma receiving the following required inhaled medications for at least 1 month prior to screening: Low doses of ICS alone, or in combination with SABA, used regularly with a stable regimen.
- •Forced Expiratory Volume in 1 second (FEV1) ≥ 80% of the local predicted normal value after withholding SABA ≥ 8 hours.
- •Airway responsiveness to methacholine demonstrated by a pre-albuterol-dose (baseline) PC20 ≤ 8 mg/mL.
- •Nonsmoker for at least 6 months prior to the study and a maximum smoking history of 5 pack-years (the equivalent of one pack per day for 5 years).
- •Provision of written informed consent.
- •Other than asthma, in general good health.
- •Body mass index (BMI) between 17 and 35 kg/m2 (inclusive).
- •Able to correctly use MDI inhalers.
Exclusion Criteria
- •Evidence of conditions altering airway reactivity to methacholine, including upper or lower respiratory tract infections (e.g., pneumonia, viral bronchitis, allergic rhinitis, sinobronchitis, etc.) within 6 weeks before Screening.
- •Evidence of a baseline FEV1 \< 60% of the local predicted normal value or FEV1 \< 1.5 L.
- •History of seasonal asthma exacerbations, in which case the subject should be studied outside of the relevant allergen season.
- •History of cystic fibrosis, bronchiectasis, COPD, or other respiratory diseases including COPD, chronic bronchitis, emphysema, tuberculosis, pulmonary carcinoma, pulmonary fibrosis, pulmonary hypertension that, in the opinion of the Investigator, would compromise subject safety or interfere with the evaluations.
- •History of cardiovascular, hematological, renal, neurologic, hepatic, psychiatric, endocrine dysfunction, including ECG with evidence of ischemic heart diseases and significant arrhythmias.
- •Treatment in an emergency room or hospitalization for acute asthmatic symptoms within 3 months prior to screening.
- •Known intolerance or hypersensitivity to any component of the albuterol MDI, beta2 receptor-agonist drug, HFA, any related compounds or methacholine.
- •Need for daily oral corticosteroids within 3 months prior to screening.
- •Cardiac arrhythmia or 12-lead electrocardiogram (ECG) abnormalities, that in the opinion of the Investigator would compromise subject safety or interfere with the evaluations, or a QTc \> 440 ms for males and \> 460 ms for females using Fredericia formula.
- •Subjects receiving beta blocker via any route or who may require beta blockers during the study.
Arms & Interventions
Placebo group
Two different Reference Placebo inhalers and two different Test Placebo inhalers
Intervention: Albuterol Sulfate inhalation Placebo
Placebo group
Two different Reference Placebo inhalers and two different Test Placebo inhalers
Intervention: Methacholine
Reference 1 group
One Reference inhaler, one Reference Placebo inhaler, and two different Test Placebo inhalers
Intervention: Albuterol Sulfate inhalation Placebo
Reference 1 group
One Reference inhaler, one Reference Placebo inhaler, and two different Test Placebo inhalers
Intervention: Methacholine
Reference 2 group
Two different Reference inhalers and two different Test Placebo inhalers
Intervention: Albuterol Sulfate inhalation Placebo
Reference 2 group
Two different Reference inhalers and two different Test Placebo inhalers
Intervention: Methacholine
Test group
One Test inhaler, one Test Placebo inhaler, and two different Reference Placebo inhalers
Intervention: Albuterol Sulfate inhalation aerosol 108 mcg per actuation
Test group
One Test inhaler, one Test Placebo inhaler, and two different Reference Placebo inhalers
Intervention: Albuterol Sulfate inhalation Placebo
Test group
One Test inhaler, one Test Placebo inhaler, and two different Reference Placebo inhalers
Intervention: Methacholine
Outcomes
Primary Outcomes
Post-dose PC20 Concentration
Time Frame: 15 minutes post-dose
Post-dose PC20, which are the provocative concentrations, respectively, of the methacholine challenge agent required to reduce the forced expiratory volume in one second (FEV1) by 20% following administration of differing concentrations of albuterol (or placebo) by inhalation.