Bioequivalence With Clinical Endpoint Study of Fluticasone Propionate 100 mcg and Salmeterol 50 mcg Inhalation Powder/Respirent Pharmaceuticals vs. ADVAIR DISKUS® 100/50 mcg Inhalation Powder/GSK in Patients With Asthma (AERO-PD)

A Phase III, Randomized, Multicenter, Parallel-group Clinical Trial for Examining the Therapeutic Equivalence Between Fluticasone Propionate 100 mcg and Salmeterol 50 mcg Inhalation Powder/Respirent Pharmaceuticals vs. ADVAIR DISKUS® 100/50 mcg Inhalation Powder/GSK in Patients With Asthma

Τherapeutic equivalence, randomized, multiple-dose, placebo-controlled, observer-blind, parallel group design consisting of a 2-week run-in period followed by a 4-week treatment period with Fluticasone propionate 100 mcg and Salmeterol 50 mcg inhalation powder/Respirent Pharmaceuticals (Test) or ADVAIR DISKUS® 100/50 mcg (Reference) or placebo.

Study Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone Propionate 100 mcg and Salmeterol 50 mcg inhalation Powder/Respirent Pharmaceuticals; Drug: ADVAIR DISKUS® 100/50 mcg inhalation powder pre-dispensed/GSK; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 451
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chrysoula Doxani, MD, MSc, PhD; Phone Number: +30 2410257310; Email: doxani@becro.gr
• Study Contact Backup: Name: Alexandra Koutarelou, MSc, PhD (Cand.); Phone Number: +30 210 6729037; Email: koutarelou@becro.gr

Study Locations

• Greece
  • Athens, Greece
    • Recruiting
    • Becro Ltd.
    • Contact: Alexandra Koutarelou; Phone Number: 6980595837; Email: koutarelou@becro.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects (≥12 years of age) of non-childbearing or of childbearing potential committed to consistent and correct use of an acceptable method of birth control.
2. Patients diagnosed with asthma, as defined by the National Asthma Education and Prevention Program (NAEPP), at least 12 weeks prior to screening.
3. Pre-bronchodilator FEV1 of ≥40% and ≤85% of the predicted value (for age ≥18 years), or ≥65% and ≤90% predicted normal value (for ages 12 to 17 years) during the screening visit and on the first day of treatment.
4. Currently non-smoking; had not used tobacco products (i.e., cigarettes, cigars, pipe tobacco) within the past year, and had ≤ 10 pack-years of historical use.
5. ≥12% and 200 mL reversibility of FEV1 within 30 minutes following 400 mcg salbutamol (4 puffs) inhalation (pMDI). This may be demonstrated at the Screening Visit or this test may be repeated on a different day if the patient fails the first attempt anytime in the period leading up to Visit 2 (randomization); If reversibility is not demonstrated up to Visit 2 then patients may be permitted to enter the study with historical evidence of reversibility that was performed within 2 years prior to Visit 1 and patients should be stable on their chronic asthma treatment regimen for at least 4 weeks prior to enrolment.
6. Patients who are able to discontinue their asthma medications (inhaled corticosteroids and long-acting β agonists) during the run-in period and for remainder of the study, according to investigator's judgement.
7. Patients who are able to replace current short-acting β agonists (SABAs) with salbutamol inhaler for use as needed for the duration of the study (subjects should be able to withhold all inhaled SABAs for at least 6 hours prior to lung function assessments on study visits).
8. Patients who are able to continue treatment with theophylline or montelukast without a significant adjustment of dosage, formulation, dosing interval for the duration of the study, and judged able by the investigator to withhold them for the specified minimum time intervals prior to each patient visit: 1) montelukast 36 hours 2) short-acting forms of theophylline 12 hours, 3) twice-a-day controlled-release forms of theophylline 24 hours, 4) once-a-day controlled-release forms of theophylline 36 hours.
9. Patients who are able to understand the requirements of the clinical trial and to agree to return for the required follow-up visits.
10. Willing to provide voluntary written informed consent and data protection declaration (and in the case of a minor their parent/guardian was able to give) before any clinical trial related procedure is performed.

Exclusion Criteria:

1. Life-threatening asthma, defined as a history of asthma episode(s) requiring intubation, and/or associated with hypercapnia; respiratory arrest or hypoxic seizures, asthma related syncopal episode(s), or hospitalizations within the past year to the screening or during the run-in period.
2. Evidence or history of clinically significant disease or abnormality including congestive heart failure, uncontrolled hypertension, uncontrolled coronary artery disease, myocardial infarction, or cardiac dysrhythmia.
3. Historical or current evidence of significant hematologic, hepatic, neurologic, psychiatric, renal, or other diseases that in the opinion of the investigator, would put the patient at risk through study participation, or would affect the study analyses if the disease exacerbated during the study.
4. Hypersensitivity to any sympathomimetic drug (e.g., salmeterol/albuterol) or to any inhaled, intranasal, or systemic corticosteroid therapy.
5. History of hypersensitivity to lactose
6. Medication(s) with the potential to affect the course of asthma or to interact with sympathomimetic amines, e.g.: β-blockers, oral decongestants, benzodiazepines, digitalis, phenothiazines, polycyclic antidepressants, monoamine oxidase inhibitors.
7. symptoms or signs of viral or bacterial, upper or lower respiratory tract infection or sinus or middle ear infection within 4 weeks prior to the screening visit or during the run-in period.
8. Asthma exacerbation (i.e. acute or sub-acute worsening in symptoms and lung function from the patient's usual status) within 6 weeks prior to the screening visit or during the run-in period
9. Use of oral or parenteral corticosteroids within 4 weeks prior to Screening visit (Visit 1)
10. Factors (e.g., infirmity, disability or geographic location) that the investigator felt would likely limit the patient's compliance with the study protocol or scheduled clinic visits.
11. Female Subjects who are pregnant or breastfeeding.
12. Women of child-bearing age that are not surgically incapable of pregnancy and are not willing to use an acceptable method of birth control.
13. Current participation or not yet completed period of at least 30 days since ending other investigational device or drug trial(s).
14. Unwillingness or inability to comply with the clinical trial procedures;
15. Unwillingness to consent to storage, saving and transmission of pseudonymous medical data for clinical trial reasons;
16. Who are legally incapacitated;
17. Who are legally detained in an official institute.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; twice daily inhalation throughout the treatment period
Experimental: Fluticasone propionate 100 mcg and Salmeterol 50 mcg inhalation powder/Respirent Pharmaceuticals; Test (T)	Drug: Fluticasone Propionate 100 mcg and Salmeterol 50 mcg inhalation Powder/Respirent Pharmaceuticals; twice daily inhalation throughout the treatment period; Other Names: Test (T)
Active Comparator: ADVAIR DISKUS® 100/50 mcg inhalation powder pre-dispensed/GSK; Reference (R)	Drug: ADVAIR DISKUS® 100/50 mcg inhalation powder pre-dispensed/GSK; twice daily inhalation throughout the treatment period; Other Names: Refernce (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 AUC (0-12h)	Area under the serial FEV1(L)-time curve calculated from time zero to 12 hours (AUC0-12h) on the first day of the treatment after adjustment for baseline (change from baseline).	12 hours
Trough FEV1	2. FEV1(L) measured in the morning prior to the dosing of inhaled medications on the last day of a 4-week (28 days) treatment (trough FEV1) after adjustment for baseline (change from baseline).	4 weeks

Collaborators and Investigators

• Sponsor: Respirent Pharmaceuticals Co Ltd.
• Collaborators: Becro Ltd.
• Investigators: Principal Investigator: Konstantinos Kostikas, Professor, University of Ioannina School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2023
• Primary Completion (Anticipated): July 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: December 15, 2022
• First Submitted That Met QC Criteria: December 15, 2022
• First Posted (Actual): December 23, 2022

Study Record Updates

• Last Update Posted (Actual): March 1, 2023
• Last Update Submitted That Met QC Criteria: February 28, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: asthma; bioequivalence; fluticasone propionate; salmeterol; therapeutic equivalence
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Respiration Disorders; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Respiratory Aspiration; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Sympathomimetics; Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination
• Other Study ID Numbers: BECRO/RESP/AERO-PD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes