Pharmacodynamic Equivalence of the Test and Reference Metered Dose Inhalers (MDIs) Containing Albuterol Sulfate in Adult Patients With Stable Mild Asthma

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

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.

Study Overview

• Status: Recruiting
• Conditions: Mild Asthma
• Intervention / Treatment: Other: Albuterol Sulfate inhalation Placebo; Other: Methacholine; Drug: Albuterol Sulfate inhalation aerosol 108 mcg per actuation; Other: Proair HFA or FDA authorized generic: Albuterol Sulfate HFA Inhalation Placebo; Drug: Proair HFA (Albuterol Sulfate) or FDA authorized generic: Albuterol Sulfate HFA (Teva Pharmaceutical USA, Inc.) Inhalation Aerosol 108 mcg per actuation

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).

• Study Type: Interventional
• Enrollment (Estimated): 148
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jasmine Kuo; Phone Number: 688 +886-2-7721-8877; Email: jasmine.i199@intechbiopharm.com

Study Locations

• India
  • Ahmedabad, India, 38007
    • Not yet recruiting
    • Dr. Jivraj Mehta Smarak Health Foundation
    • Contact: Vaishal Sheth
    • Principal Investigator: Vaishal Sheth
  • Belagave, India, 590010
    • Not yet recruiting
    • KLEs Dr Prabhakar Kore Hospital & MRC
    • Contact: Jyothi Hattiholi
    • Principal Investigator: Jyothi Hattiholi
  • Kolkata, India, 700014
    • Not yet recruiting
    • NRS Medical College and Hospital
    • Principal Investigator: Jaydip Deb
    • Contact: Jaydip Deb
  • Kolkata, India, 700073
    • Not yet recruiting
    • Medical College and Hospital
    • Contact: Kaushik Saha
    • Principal Investigator: Kaushik Saha
  • New Delhi, India, 110075
    • Not yet recruiting
    • Aakash Healthcare Super Specialty Hospital
    • Contact: Akshay Budhraja
    • Principal Investigator: Akshay Budhraja
  • Pune, India, 411018
    • Not yet recruiting
    • Pimpri Chinchwad Municipal Corporation Post Graduate Institute Yashwantrao Chavan Memorial Hospital
    • Contact: Pravin Soni
    • Principal Investigator: Pravin Soni
  • Pune, India, 411038
    • Not yet recruiting
    • Kothrud Hospital
    • Contact: Himanshu Pophale
    • Principal Investigator: Himanshu Pophale
  • Ulhasnagar, India, 421004
    • Not yet recruiting
    • Ashirwad Hospital and Research Centre
    • Contact: Shrikant Vishnu Deshpande
    • Principal Investigator: Shrikant Vishnu Deshpande
• Taiwan
  • Kaohsiung City, Taiwan, 807
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
    • Contact: Chau-Chyun Sheu, MD
    • Principal Investigator: Chau-Chyun Sheu, MD
  • New Taipei City, Taiwan, 251
    • Recruiting
    • Tamshui Mackay Memorial Hospital
    • Contact: Hsin-Pei Chung, MD
    • Principal Investigator: Hsin-Pei Chung, MD
  • Taipei City, Taiwan, 110
    • Recruiting
    • Taipei Medical University Hospital
    • Contact: Pai-Chien Chou, MD, PhD
    • Principal Investigator: Pai-Chien Chou, MD, PhD
  • Taipei City, Taiwan, 111
    • Recruiting
    • Shin Kong Wu Ho-Su Memorial Hospital
    • Contact: Shih-Sen Lin, MD
    • Principal Investigator: Shih-Sen Lin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male, non-pregnant and non-lactating female subjects (20-65 years of age, inclusive).
2. 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).
3. 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.
4. Forced Expiratory Volume in 1 second (FEV1) ≥ 80% of the local predicted normal value after withholding SABA ≥ 8 hours.
5. Airway responsiveness to methacholine demonstrated by a pre-albuterol-dose (baseline) PC20 ≤ 8 mg/mL.
6. 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).
7. Provision of written informed consent.
8. Other than asthma, in general good health.
9. Body mass index (BMI) between 17 and 35 kg/m2 (inclusive).
10. Able to correctly use MDI inhalers.
11. Able to perform valid and reproducible pulmonary function tests including no evidence of spirometry effort-induced bronchoconstriction.
12. If the subject or subject's partner is of child-bearing potential, a medically acceptable form of contraception will be used for the duration of the study. Medically acceptable contraceptives include: (1) surgical sterilization, (2) Health Authority approved female hormonal contraceptives, (3) an intrauterine device (IUD), (4) condoms with spermicide, or (5) diaphragm with spermicide.

Exclusion Criteria:

1. 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.
2. Evidence of a baseline FEV1 < 60% of the local predicted normal value or FEV1 < 1.5 L.
3. History of seasonal asthma exacerbations, in which case the subject should be studied outside of the relevant allergen season.
4. 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.
5. History of cardiovascular, hematological, renal, neurologic, hepatic, psychiatric, endocrine dysfunction, including ECG with evidence of ischemic heart diseases and significant arrhythmias.
6. Treatment in an emergency room or hospitalization for acute asthmatic symptoms within 3 months prior to screening.
7. Known intolerance or hypersensitivity to any component of the albuterol MDI, beta2 receptor-agonist drug, HFA, any related compounds or methacholine.
8. Need for daily oral corticosteroids within 3 months prior to screening.
9. 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.
10. Subjects receiving beta blocker via any route or who may require beta blockers during the study.
11. History of narrow angle glaucoma, convulsive disorders, hyperthyroidism, uncontrolled diabetes, paradoxical bronchospasm.
12. History of malignancies.
13. History of alcohol or drug abuse.
14. Eye, brain, thoracic, and abdominal surgeries within 3 months prior to screening.
15. Use of cromyolyn, leukotriene receptor antagonists (LTRA), nedocromil, zileuton, theophylline, or long-acting beta-agonists (LABA) within 1 month prior to screening.
16. History of receiving muscarinic beta2-agonists (MABAs), short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), anti-IgE, anti-IL5/5R, anti-IL4R, high dose ICS, or systemic corticosteroid for treatment of asthma within 6 months prior to screening.
17. Known Human Immunodeficiency Virus (HIV)-positive status.
18. Participated in any interventional clinical trials within 1 month prior to screening.
19. Pregnancy or breast feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group; Two different Reference Placebo inhalers and two different Test Placebo inhalers	Other: Albuterol Sulfate inhalation Placebo; MDI; Other: Methacholine; Methacholine 100 mg/vial; Other: Proair HFA or FDA authorized generic: Albuterol Sulfate HFA Inhalation Placebo; MDI
Active Comparator: Reference 1 group; One Reference inhaler, one Reference Placebo inhaler, and two different Test Placebo inhalers	Other: Albuterol Sulfate inhalation Placebo; MDI; Other: Methacholine; Methacholine 100 mg/vial; Other: Proair HFA or FDA authorized generic: Albuterol Sulfate HFA Inhalation Placebo; MDI; Drug: Proair HFA (Albuterol Sulfate) or FDA authorized generic: Albuterol Sulfate HFA (Teva Pharmaceutical USA, Inc.) Inhalation Aerosol 108 mcg per actuation; equal to albuterol 90 mcg/puff, MDI; Other Names: Albuterol Sulfate
Active Comparator: Reference 2 group; Two different Reference inhalers and two different Test Placebo inhalers	Other: Albuterol Sulfate inhalation Placebo; MDI; Other: Methacholine; Methacholine 100 mg/vial; Drug: Proair HFA (Albuterol Sulfate) or FDA authorized generic: Albuterol Sulfate HFA (Teva Pharmaceutical USA, Inc.) Inhalation Aerosol 108 mcg per actuation; equal to albuterol 90 mcg/puff, MDI; Other Names: Albuterol Sulfate
Experimental: Test group; One Test inhaler, one Test Placebo inhaler, and two different Reference Placebo inhalers	Other: Albuterol Sulfate inhalation Placebo; MDI; Other: Methacholine; Methacholine 100 mg/vial; Drug: Albuterol Sulfate inhalation aerosol 108 mcg per actuation; equal to albuterol 90 mcg/puff, MDI; Other Names: Albuterol Sulfate; Other: Proair HFA or FDA authorized generic: Albuterol Sulfate HFA Inhalation Placebo; MDI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-dose PC20 Concentration	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.	15 minutes post-dose

Collaborators and Investigators

• Sponsor: Intech Biopharm Ltd.
• Investigators: Principal Investigator: Pai-Chien Chou, MD, PhD, Taipei Medical University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2022
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: May 28, 2021
• First Submitted That Met QC Criteria: May 28, 2021
• First Posted (Actual): June 3, 2021

Study Record Updates

• Last Update Posted (Actual): February 8, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Adrenergic Agonists; Cholinergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Miotics; Parasympathomimetics; Bronchoconstrictor Agents; Muscarinic Agonists; Albuterol; Methacholine Chloride; Procaterol
• Other Study ID Numbers: TW20-4643

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No