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

NCT04912596 | Recruiting

• 1 other identifier: TW20-4643
• Study Type: interventional
• Target: 148
• Locations: 2 countries
• Sites: 12

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.

Conditions

Mild Asthma

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (4)

Placebo group

PLACEBO COMPARATOR

Two different Reference Placebo inhalers and two different Test Placebo inhalers

Other: Proair HFA or FDA authorized generic: Albuterol Sulfate HFA Inhalation Placebo; Other: Albuterol Sulfate inhalation Placebo; Other: Methacholine

Reference 1 group

ACTIVE COMPARATOR

One Reference inhaler, one Reference Placebo inhaler, and two different Test Placebo inhalers

Drug: Proair HFA (Albuterol Sulfate) or FDA authorized generic: Albuterol Sulfate HFA (Teva Pharmaceutical USA, Inc.) Inhalation Aerosol 108 mcg per actuation; Other: Proair HFA or FDA authorized generic: Albuterol Sulfate HFA Inhalation Placebo; Other: Albuterol Sulfate inhalation Placebo; Other: Methacholine

Reference 2 group

ACTIVE COMPARATOR

Two different Reference inhalers and two different Test Placebo inhalers

Drug: Proair HFA (Albuterol Sulfate) or FDA authorized generic: Albuterol Sulfate HFA (Teva Pharmaceutical USA, Inc.) Inhalation Aerosol 108 mcg per actuation; Other: Albuterol Sulfate inhalation Placebo; Other: Methacholine

Test group

EXPERIMENTAL

One Test inhaler, one Test Placebo inhaler, and two different Reference Placebo inhalers

Drug: Albuterol Sulfate inhalation aerosol 108 mcg per actuation; Other: Proair HFA or FDA authorized generic: Albuterol Sulfate HFA Inhalation Placebo; Other: Albuterol Sulfate inhalation Placebo; Other: Methacholine

Interventions

Albuterol Sulfate inhalation aerosol 108 mcg per actuation DRUG

equal to albuterol 90 mcg/puff, MDI

Also known as: Albuterol Sulfate

Test group

Proair HFA (Albuterol Sulfate) or FDA authorized generic: Albuterol Sulfate HFA (Teva Pharmaceutical USA, Inc.) Inhalation Aerosol 108 mcg per actuation DRUG

equal to albuterol 90 mcg/puff, MDI

Also known as: Albuterol Sulfate

Reference 1 group; Reference 2 group

Proair HFA or FDA authorized generic: Albuterol Sulfate HFA Inhalation Placebo OTHER

MDI

Placebo group; Reference 1 group; Test group

Albuterol Sulfate inhalation Placebo OTHER

MDI

Placebo group; Reference 1 group; Reference 2 group; Test group

Methacholine OTHER

Methacholine 100 mg/vial

Placebo group; Reference 1 group; Reference 2 group; Test group

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Able to perform valid and reproducible pulmonary function tests including no evidence of spirometry effort-induced bronchoconstriction.
• 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.

You may not qualify if:

• 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.
• History of narrow angle glaucoma, convulsive disorders, hyperthyroidism, uncontrolled diabetes, paradoxical bronchospasm.
• History of malignancies.
• History of alcohol or drug abuse.
• Eye, brain, thoracic, and abdominal surgeries within 3 months prior to screening.
• Use of cromyolyn, leukotriene receptor antagonists (LTRA), nedocromil, zileuton, theophylline, or long-acting beta-agonists (LABA) within 1 month prior to screening.

Sponsors & Collaborators

• Intech Biopharm Ltd.: lead

Study Sites (12)

Dr. Jivraj Mehta Smarak Health Foundation

Ahmedabad, 38007, India

NOT YET RECRUITING

KLEs Dr Prabhakar Kore Hospital & MRC

Belagāve, 590010, India

NOT YET RECRUITING

NRS Medical College and Hospital

Kolkata, 700014, India

NOT YET RECRUITING

Medical College and Hospital

Kolkata, 700073, India

NOT YET RECRUITING

Aakash Healthcare Super Specialty Hospital

New Delhi, 110075, India

NOT YET RECRUITING

Pimpri Chinchwad Municipal Corporation Post Graduate Institute Yashwantrao Chavan Memorial Hospital

Pune, 411018, India

NOT YET RECRUITING

Kothrud Hospital

Pune, 411038, India

NOT YET RECRUITING

Ashirwad Hospital and Research Centre

Ulhasnagar, 421004, India

NOT YET RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 807, Taiwan

RECRUITING

Tamshui Mackay Memorial Hospital

New Taipei City, 251, Taiwan

RECRUITING

Taipei Medical University Hospital

Taipei, 110, Taiwan

RECRUITING

Shin Kong Wu Ho-Su Memorial Hospital

Taipei, 111, Taiwan

RECRUITING

MeSH Terms

Interventions

Albuterol; Methacholine Chloride

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Phenethylamines; Ethylamines; Methacholine Compounds; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds

Study Officials

• Pai-Chien Chou, MD, PhD

  Taipei Medical University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jasmine Kuo

CONTACT

+886-2-7721-8877; jasmine.i199@intechbiopharm.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 3, 2021
• Study Start: August 15, 2022
• Primary Completion: January 31, 2025
• Study Completion: June 1, 2025
• Last Updated: February 17, 2025

Record last verified: 2025-02

Locations

TW (4); IN (8)