Journal Article

A Novel Metered Dose Inhaler Formulation of Triple-Drug Fixed-Dose Combination of Vilanterol, Glycopyrronium, and Fluticasone Furoate: A Phase III, Randomized, Multicenter Trial to Evaluate the Efficacy and Safety in Indian Patients With Uncontrolled Asthma

Verma, Sanjay, Parmar, Deven, Sheth, Vaishal, Sahoo, Diptikant, Jain, Manish Kumar, Koppula, Ravi, Panda, Jayanta Kumar, Kumar, Deepak, Patel, Chintan, Pathak, Hardik, Kansagra, Kevinkumar

2025

Overview

•Persistent asthma may be better controlled by adding a long-acting muscarinic antagonist to inhaled corticosteroid + long-acting β agonist combination.•Metered dose inhaler of a novel long-acting muscarinic antagonist + long-acting β agonist + inhaled corticosteroid combination is tested.•Vilanterol 25 µg, glycopyrronium 50 µg, and fluticasone furoate 200 µg were tested.•Indacaterol 150 µg, glycopyrronium 50 µg, and mometasone furoate 160 µg were used as reference.•Test drugs were found to be noninferior to reference drugs.•Test drugs were well tolerated. This study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of vilanterol 12.5 µg, glycopyrronium 25 µg, and fluticasone furoate 100 µg (VIL-GLY-FF)–metered dose inhaler (MDI) (developed by M/s. Zydus Healthcare Limited) in comparison with the approved FDC of indacaterol 150 µg, glycopyrronium 50 µg, and mometasone furoate 160 µg (IND-GLY-MF)–dry powder inhaler (DPI) in patients with persistent asthma. Patients were randomized (1:1) in either the test (VIL-GLY-FF-MDI) or reference (IND-GLY-MF-DPI) group. Fixed-dose combinations were administered once daily for 12 weeks; for VIL-GLY-FF-MDI, patients were instructed to administer TWO actuations at 1 time in a day, doubling the final doses delivered of its components. For IND-GLY-MF-DPI, (Zydus Healthcare Limited, Ahmedabad) patients inhaled 1 capsule via the Respihaler device once daily. The primary objective was to compare the between-group difference in the change in trough forced expiratory volume in 1 second (FEV1) at week 12 from baseline. A total of 256 patients were enrolled. The change in least square mean (SE) in trough FEV1 at week 12 from baseline was 287.15 (18.00) mL and 284.94 (17.93) mL for the test and reference groups, respectively. For a predefined −150 mL noninferiority margin, 2-sided 95% CIs (−47.83 to 52.26 mL) for the difference in the mean change in trough FEV1 (2.21 mL) between the 2 groups reported the noninferiority of VIL-GLY-FF-MDI to IND-GLY-MF-DPI. The test FDC was well tolerated. Efficacy and safety of VIL-GLY-FF-MDI were found to be similar to those of IND-GLY-MF-DPI in Indian patients with persistent asthma. Clinical Trial Registry India identifier: CTRI/2024/01/061230.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Administration, Inhalation / Adult / Androstadienes - administration & dosage / Androstadienes - adverse effects / Androstadienes - therapeutic use / Anti-Asthmatic Agents - administration & dosage / Anti-Asthmatic Agents - adverse effects / Asthma / Asthma - drug therapy / Asthma - physiopathology / Benzyl Alcohols - administration & dosage / Benzyl Alcohols - adverse effects / Benzyl Alcohols - therapeutic use / Bronchodilator Agents - administration & dosage / Bronchodilator Agents - adverse effects / Chlorobenzenes - administration & dosage / Chlorobenzenes - adverse effects / Chlorobenzenes - therapeutic use / Clinical trials / Drug Combinations / Drug dosages / Dry Powder Inhalers / Female / Fluticasone / Fluticasone Furoate / Forced Expiratory Volume / Glycopyrrolate - administration & dosage / Glycopyrrolate - adverse effects / Glycopyrrolate - therapeutic use / Glycopyrronium / Health care / Humans / India / Inhalers / Internal Medicine / Male / Metered Dose Inhalers / Middle Aged / Patient safety / Patients / Pharmaceuticals / Phase III / Randomized / Self-efficacy / Statistical analysis / Steroids / Treatment Outcome / Vilanterol / Young Adult