SESSION TYPE: COPD: Safety and Effectiveness of Newer Therapies
PRESENTED ON: Tuesday, October 23, 2012 at 02:45 PM - 04:15 PM
PURPOSE: Aclidinium is a novel, long-acting, muscarinic antagonist in development for the maintenance treatment of COPD. This report includes pooled safety data from 2 Phase III, placebo-controlled studies (12-week ACCORD I, 24-week ATTAIN) of twice-daily (BID) aclidinium 200 µg and 400 µg in moderate-to-severe COPD patients.
METHODS: In these double-blind trials, patients were randomized (1:1:1) to aclidinium 200 µg, 400 µg, or placebo BID. Safety was assessed via adverse events (AEs), laboratory measures, and vital signs.
RESULTS: A total of 1389 patients were randomized in both studies and 1379 patients were included in the pooled safety population of ACCORD I (N=560) and ATTAIN (N=819). Treatment-emergent adverse events (TEAEs) were generally mild or moderate in severity and occurred in a lower percentage of patients in the 200 µg and 400 µg groups (52.9% and 49.9%, respectively) vs placebo (55.1%). COPD exacerbation was the most frequently reported TEAE (17.2% for placebo, 13.2% for aclidinium 200 µg, and 11.3% for aclidinium 400 µg). Incidences of anticholinergic events such as dry mouth and constipation were low (<2% for any group) and most events were reported by the lowest proportion of patients in the aclidinium 400 µg treatment group. The proportion of patients who discontinued from the studies due to a TEAE was highest in the placebo group (5.4%) and lowest in the aclidinium 400 µg group (3.5%), with COPD exacerbation as the most frequent reason for discontinuation. The incidence of serious AEs was low and similar across groups (<5% for any group). Cardiac events were infrequent and reported by <5% of patients for any group. A numerical imbalance was observed for cardiac failure between placebo (0.4%) and aclidinium 400 µg (0.9%); however, most of the patients in the aclidinium 400 µg group who reported these events had a baseline medical condition that could have contributed to the event. Four treatment-emergent deaths were reported (placebo, 1 [0.2%]; 200 µg, 1 [0.2%]; 400 µg, 2 [0.4%]), 2 of which were cardiac-related (200 µg, 1; 400 µg, 1); none were considered related to treatment. No clinically relevant changes were observed in laboratory measures and vital signs for any group.
CONCLUSIONS: The safety profiles of both aclidinium doses were comparable to placebo and similar between doses in both studies.
CLINICAL IMPLICATIONS: Results from these pivotal studies demonstrate that twice-daily aclidinium is well tolerated and may be a valuable new treatment option for patients with COPD.
DISCLOSURE: Edward Kerwin: Consultant fee, speaker bureau, advisory committee, etc.: Consultant
Stephen Rennard: Consultant fee, speaker bureau, advisory committee, etc.: Consultant
James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: Consultant
Bart Celli: Consultant fee, speaker bureau, advisory committee, etc.: Consultant
Ludmyla Rekeda: Employee: Employee of Forest Research Institute
Esther Garcia Gil: Employee: Employee of Almirall S.A.
Cynthia Caracta: Employee: Employee of Forest Research Institute
Aclidinium is currently under FDA review for the treatment of COPD.Clinical Research Institute, Medford, OR