Dual Bronchodilation with Indacaterol Maleate/Glycopyrronium Bromide Compared with Umeclidinium Bromide/Vilanterol in Patients with Moderate-to-Severe COPD: Results from Two Randomized, Controlled, Cross-over Studies

摘要

Abstract Purpose To compare the efficacy and safety of two long-acting dual bronchodilator combinations: indacaterol/glycopyrrolate (IND/GLY) versus umeclidinium/vilanterol (UMEC/VI). Methods Studies A2349 and A2350 were replicate, randomized, double-blind, double-dummy, active-controlled, cross-over studies in patients with moderate-to-severe COPD. Patients were randomized to sequential 12-week treatments of twice-daily IND/GLY 27.5/15.6?μg and once-daily UMEC/VI 62.5/25?μg, each separated by a 3-week washout. The primary objective was to demonstrate non-inferiority of IND/GLY compared with UMEC/VI in terms of the 24-h forced expiratory volume in 1?s profile at week 12 (FEV 1 AUC 0–24 ). Rescue medication use, symptom control, and safety were assessed throughout. Results Both treatments delivered substantial bronchodilation over 12?weeks, with improvements in FEV 1 AUC 0–24h at week 12 of 232 and 185?mL for IND/GLY, and 244 and 203?mL with UMEC/VI in Studies A2349 and A2350, respectively. The primary efficacy objective of non-inferiority of IND/GLY relative to UMEC/VI was not met as the lower bound of the confidence interval for the LS treatment comparison was below the pre-specified non-inferiority margin of ?20?mL in both studies: ?26.9 and ?34.2?mL, respectively (LS mean between-treatment differences: ?11.5 and ?18.2?mL). Both drugs were well tolerated, with AE profiles consistent with their respective prescribing information. Conclusions IND/GLY and UMEC/VI provided clinically meaningful and comparable bronchodilation. Non-inferiority of IND/GLY to UMEC/VI could not be declared although between-treatment differences were not clinically relevant. The data support the use of IND/GLY as an efficacious and well tolerated treatment option in patients with COPD. (ClinicalTrials.gov NCT02487446 and NCT02487498)