Respiratory medicine | 2019
Revefenacin, a once-daily, lung-selective, long-acting muscarinic antagonist for nebulized therapy: Safety and tolerability results of a 52-week phase 3 trial in moderate to very severe chronic obstructive pulmonary disease.
Abstract
BACKGROUND\nPrior replicate 12-week phase 3 trials demonstrated that once-daily doses of revefenacin inhalation solution at 88\u202fμg and 175\u202fμg produced significant bronchodilation over 24\u202fh post dose in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). The objective was to characterize the safety profile of revefenacin 88\u202fμg and 175\u202fμg over 52 weeks of treatment.\n\n\nMETHODS\nIn this randomized, parallel-group, 52-week trial (NCT02518139), 1055 participants with moderate to very severe COPD received revefenacin 88\u202fμg or 175\u202fμg in a double-blind manner, or open-label active control tiotropium.\n\n\nRESULTS\nTreatment-emergent adverse events (AEs) were comparable across all treatment groups (n [%] patients; revefenacin 88\u202fμg, 272 [74.7%]; 175\u202fμg, 242 [72.2%]; tiotropium, 275 [77.2%]). Numerically fewer COPD exacerbations (n [%] patients) were observed with revefenacin 175\u202fμg (73 [21.8%]) than with 88\u202fμg (107 [29.4%]) or tiotropium (100 [28.1%]). Serious AEs were comparable with revefenacin 88\u202fμg (58 [15.9%] and tiotropium (58 [16.3%]), but were lower with revefenacin 175\u202fμg (43 [12.8%]), and mortality was low. In patients using revefenacin 88\u202fμg or tiotropium with a concurrent long-acting β-agonist (LABA) product, the incidence of AEs was slightly higher than without concurrent LABA. LABA did not affect the incidence of AEs for patients who received revefenacin 175\u202fμg.\n\n\nCONCLUSIONS\nRevefenacin was generally well tolerated over 52 weeks of treatment, and had a safety profile that supports its use as a long-term once-daily bronchodilator for the nebulized treatment of COPD.