Efficacy and Safety of Revefenacin Versus Glycopyrronium in Indian Chronic Obstructive Pulmonary Disease (COPD) Patients: A Randomized, Active-Controlled, Phase III Trial

BackgroundChronic obstructive pulmonary disease (COPD) affects 50-55 million individuals in India.Long-acting muscarinic antagonists (LAMAs) are a cornerstone of maintenance pharmacotherapy according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations.Revefenacin, a once-daily nebulized LAMA approved by the US FDA in 2018, lacks clinical evidence in Indian patients.This phase III study evaluated the efficacy and safety of revefenacin 175 mcg versus glycopyrronium 25 mcg in patients with moderate-to-very-severe COPD. MethodsThis prospective, randomized, open-label, active-controlled, multicenter phase III trial enrolled participants aged ≥40 years with moderate-to-very-severe COPD (post-bronchodilator FEV₁/FVC <0.70; FEV₁ <80% predicted) and a smoking history of ≥10 pack-years across 10 sites in India (Clinical Trials Registry-India: CTRI/2025/06/089258). Participants were randomized 1:1 to receive revefenacin 175 mcg once daily (n=121) or glycopyrronium 25 mcg twice daily (n=121) for 12 weeks.The primary endpoint was the change from baseline (CFB) in trough FEV₁ at week 12. Secondary endpoints included peak FEV₁ and FVC on day 1, trough FEV₁ at week 4, trough FVC at weeks four and 12, and the St. George's Respiratory Questionnaire (SGRQ) responder rate at week 12. Safety was assessed based on adverse events (AEs), vital signs, ECG findings, and laboratory parameters.Analysis of covariance (ANCOVA) was used, with comparability defined as p≥0.05. ResultsOf the 242 randomized participants, 233 (96.3%) completed the study.Baseline characteristics were well balanced (mean age, 56.4 years; moderate COPD, 61.2%; severe COPD, 36.8%).The mean CFB in trough FEV₁ at week 12 was 256.3±232.32mL for revefenacin and 251.8±265.14mL for glycopyrronium (perprotocol population); the least squares (LS) mean difference was 4.5 mL (95% CI, -58.21 to 67.16; p=0.89).Secondary endpoints showed no significant between-group differences in peak FEV₁ (p=0.87),peak FVC (p=0.30),trough FEV₁ at week 4 (p=0.37),trough FVC at week 4 (p=0.81)and 12 (p=0.98),or SGRQ responder rate (87.2% vs. 84.8%;OR, 1.21; p=0.69).No deaths or serious AEs occurred.AE incidence was 11.57% with revefenacin and 12.40% with glycopyrronium.All events were mild to moderate, with no discontinuations due to AEs. ConclusionRevefenacin 175 mcg once daily demonstrated comparable efficacy and safety to glycopyrronium 25 mcg twice daily in Indian patients with COPD, supporting its use as a once-daily nebulized LAMA for COPD management in India.