A Phase 3 Randomized Controlled Trial of Fixed-Dose Vilanterol/Umeclidinium/Fluticasone Furoate Versus Indacaterol/Glycopyrronium/Mometasone Furoate Dry Powder Inhalers in Indian Adults With Asthma

Background and objectiveA novel fixed-dose combination (FDC) of vilanterol 25 µg, umeclidinium 62.5 µg, and fluticasone furoate 200 µg (VIL-UME-FF) in a dry powder inhaler (DPI) formulation has been developed by Zydus Healthcare Limited (Ahmedabad, India) for the management of persistent asthma.This trial aimed to compare its efficacy and safety with those of an approved triple-combination DPI formulation. MethodsIn this phase 3, multicenter, parallel-group, open-label trial, patients with persistent asthma were randomized (1:1) to receive either the test VIL-UME-FF DPI or the reference DPI containing indacaterol 150 µg, glycopyrronium 50 µg, and mometasone furoate 160 µg (IND-GLY-MF), which was approved by the Drugs Controller General of India.Both treatments were administered once daily for 12 weeks.The primary endpoint was the change from baseline in trough forced expiratory volume in one second (FEV1) at week 12, which was analyzed using analysis of covariance in the per-protocol population (non-inferiority margin, -150 mL).Secondary endpoints included trough forced vital capacity (FVC), post-bronchodilator FEV1 and FVC, Asthma Control Test score, rescue medication-free days, and asthma exacerbations. ResultsOf 258 randomized patients aged 18-65 years (test: 129; reference: 129), 257 (test: 129; reference: 128) were included in the per-protocol population.The least squares mean (standard error) change from baseline in trough FEV1 at week 12 was 342.9 (21.27) mL in the test group and 327.6 (21.35) mL in the reference group (difference: 15.2 mL; 95% confidence interval (CI): -44.19 to 74.64 mL; p = 0.6141).The lower limit of the 95% CI was well above the prespecified non-inferiority margin of -150 mL.No statistically significant between-group differences were observed in the secondary efficacy endpoints.Additionally, there were no deaths or serious treatment-emergent adverse events in either group. ConclusionsVIL-UME-FF DPI was non-inferior to IND-GLY-MF DPI in improving trough FEV1, demonstrated no statistically significant differences in secondary efficacy endpoints, and was well tolerated in Indian patients with persistent asthma.