To evaluate the Pharmacodynamic Equivalence of the Test and Reference Metered Dose Inhalers Containing Albuterol Sulfate in Adult Patients with Stable Mild Asthma
Scientific Title of Study
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.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
TW20-4643, V1.8 dated 5 Oct 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Shrikant Deshpande
Designation
Principal Investigator
Affiliation
Aashirwad Hospital and Research Centre
Address
Aashirwad Hospital and Research Centre, Department of General Medicine, OPD No 01, Ground floor, next to Jijamata Udyan, Maratha Section 32, Krishna Nagar,
Thane MAHARASHTRA 421004 India
Phone
9822017445
Fax
Email
writetoshrikant@rediffmail.com
Details of Contact Person Scientific Query
Name
Kanhaiya Choudhary
Designation
Clinical Operations Director
Affiliation
Novotech Clinical Research India Private Limited
Address
Ground Floor, Unit 1,Block E, Helios Business Park. Bangalore 560103 India
Bangalore KARNATAKA 560103 India
Phone
9538924190
Fax
Email
Kanhaiya.Choudhary@novotech-cro.com
Details of Contact Person Public Query
Name
Kanhaiya Choudhary
Designation
Clinical Operations Director
Affiliation
Novotech Clinical Research India Private Limited
Address
Ground Floor, Unit 1,Block E, Helios Business Park. Bangalore 560103 India
408, Level 4 East Patel Nagar, New Delhi (India)-110008
Countries of Recruitment
India
Sites of Study
No of Sites = 8
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Akshay Budhraja
Aakash Healthcare Super Specialty Hospital
Aakash Healthcare Super Specialty Hospital
Department of academics and Clinical Research, Block III, Hospital Plot, Road No.201, Sector-3, Dwarka, New Delhi-110075
New Delhi DELHI
011-43388888
drakshay.budhraja@aakashhealthcare.com
Dr Shrikant Deshpande
Aashirwad Hospital and Research Centre
Aashirwad Hospital and Research Centre, Department of General Medicine, OPD No 01 Ground Floor, next to Jijamata Udyan, Maratha Section 32, Krishna Nagar, Thane MAHARASHTRA
9822017445
writetoshrikant@rediffmail.com
Dr Vaishal Seth
Dr Jivraj Mehta Smarak Health Foundation
Dr. Jivraj Mehta Smarak Health Foundation, Bakeri Medical Research Centre, Ratubhai Adani Arogyadham, Dr. Jivraj Mehta Marg, Ahmedabad, 380007, Gujarat, India Ahmadabad GUJARAT
9925965133
vaishalsheth1@gmail.com
Dr Jyothi Hattiholi
KLEs Dr. Prabhakar Kore Hospital & Medical Research Centre
Dr Jyothi Hattiholi
KLEs Dr. Prabhakar Kore Hospital & Medical Research Centre, Department of Respiratory Medicine, OPD Room Number 18,
Front Entrance, NH Service Road, Chikodi Back Entrance,
Nehru Nagar,
Belagavi, Karnataka- 590010
India.
Belgaum KARNATAKA
9164012011
pulmojyoti@gmail.com
Dr Himanshu Pophale
Kothrud Hospital
Kothrud Hospital
Clinical Research Department, Ground Floor, Gadiya Estate, Opposite Hill View Park, Bhagya Chintamani Nagar,
Guruganesh Nagar, Kothrud, Pune,
Maharastra 411038
Pune MAHARASHTRA
7588693308
himanshupophale@yahoo.co.in
Dr Kaushik Saha
Medical College, Kolkata
Medical College Kolkatta, Department of Respiratory Medicine, Faculty room,
88, College St, Calcutta Medical College, College Square, Kolkata- 700073 Kolkata WEST BENGAL
9433383080
drksaha@icloud.com
Dr Jaydip Deb
NRS Medical College and Hospital
Department of Chest and Respiratory Medicine
Nilratan Sircar Medical College & Hospital
138, AJC Bose Road
Kolkatta-700014, West Bengal
Kolkata WEST BENGAL
91-9007723918
drdebalina2@indorivclinical.com
Dr Pravin Soni
Yashwantrao Chavan Memorial Hospital
Department of Research, Ground florr, Sant Tukaram Nagar, Pimpri, Pune 411018, Maharashtra, India. Pune MAHARASHTRA
Aakash Healthcare Super Specialty Hospital Institutional Ethics Committee
Approved
Ashirwad Ethics Committtee
Approved
Dr. Jivraj Mehta Smarak Health Foundation, Bakeri Medical Research Centre Institutional Ethics Committee
Approved
Ethics Committee Nil Ratan Sircar Medical College
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee
Not Applicable
Institutional Ethics Committee Sai-Sneh Hospital and Diagnostic CenterĂ‚Â
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: J00-J99||Diseases of the respiratory system,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Albuterol Sulfate
Albuterol Sulfate inhalation aerosol 108 mcg per actuation Route of administration- Inhalation, Once a day
Comparator Agent
Albuterol Sulfate HFA
ProAir HFA (albuterol sulfate) or FDA authorized generic: Albuterol Sulfate HFA (Teva Pharmaceutical USA, Inc.) Inhalation Aerosol 108 mcg per actuation, once a day
Comparator Agent
Reference Placebo
Reference Placebo, once a day
Intervention
Test Placebo
Test placebo, once a day
Inclusion Criteria
Age From
20.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Male, nonpregnant and nonlactating female subjects (20 to 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) greater than or equal to 80 percentage of the local predicted normal value after withholding SABA greater than or equal to 8 hours.
5. Airway responsiveness to methacholine demonstrated by a pre albuterol dose (baseline) PC20 smaller than or equal to 8 mg per 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 per 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 subjects partner is of childbearing potential, a medically acceptable form of contraception will be used for the duration of the study. Medically acceptable contraceptives including (1) surgical sterilization, (2) Health Authority approved female hormonal contraceptives, (3) an intrauterine device (IUD), (4) condoms with spermicide, or (5) diaphragm with spermicide.
ExclusionCriteria
Details
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 less than 60 percentage of the local predicted normal value or FEV1 less than 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 more than 440 ms for males and more than 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, 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.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
To evaluate PD profile of the test product of albuterol sulfate inhalation aerosol 108 mcg per actuation (equivalent to 90 mcg of albuterol base) and to determine its bioequivalence to the PD profile of RLD in adult patients with stable mild asthma
Visit 1 to Visit 5
Secondary Outcome
Outcome
TimePoints
To assess the safety profile of the test product compared to that of the reference product. Safety parameters, such as AEs and vital signs (BP, PR, and body temperature).
Screening to Visit 5
Target Sample Size
Total Sample Size="110" Sample Size from India="110" Final Enrollment numbers achieved (Total)= "102" Final Enrollment numbers achieved (India)="102"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is a single-dose, randomized, double blind, double dummy, four-sequence, four-treatment, and multi-centre study design to assess 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). Each subject will participate in for a minimum of 14 days and up to a maximum of 42 days, including a Screening Period and a telephone call 3 to 7 days after the final dose of study drug.