SESSION TYPE: COPD: Safety and Effectiveness of Newer Therapies
PRESENTED ON: Tuesday, October 23, 2012 at 02:45 PM - 04:15 PM
PURPOSE: Aclidinium bromide is a novel, long-acting, muscarinic antagonist currently under investigation for the maintenance treatment of COPD. Safety data from 2 long-term, double-blind studies (CL35 and CL36) of twice-daily (BID) aclidinium 200 µg and 400 µg in moderate-to-severe COPD patients are reported here.
METHODS: In these 52-week, double-blind trials, patients were randomized to aclidinium 200 µg or 400 µg BID, administered via a multidose dry-powder inhaler (Genuair®*). Safety was assessed via adverse events (AEs), laboratory measures, and vital signs.
RESULTS: A total of 896 patients were randomized to these long-term studies and 891 were included in the safety population. The percentages of patients who reported ≥1 treatment-emergent AE (TEAE) were similar across groups (200 µg, 67.0%; 400 µg, 68.6%). COPD exacerbation was the most frequently reported TEAE, serious AE, and AE leading to discontinuation; these were all reported by a similar percentage of patients in each treatment group. Percentages of patients who discontinued from the study were similar across treatments (overall discontinuations due to a TEAE: 200 µg, 11.2%; 400 µg, 9.5%) and were <0.5% for any TEAE by preferred term, excluding COPD exacerbation, in either treatment group. No dose-response in discontinuations was observed. Incidences of anticholinergic AEs that are commonly reported with LAMAs (ie, dry mouth and constipation) were low with <3.5% reported for any treatment group. Major adverse cardiac events (MACE) were low in both groups. The MACE composite score (total number of cardiovascular deaths, nonfatal myocardial infarctions, and nonfatal strokes reported per treatment group) was lower with aclidinium 400 µg (1.4%) vs the 200 µg group (1.6%), suggesting no dose-dependent effects. Three deaths occurred in the aclidinium 200 µg group and 2 in the aclidinium 400 µg group; none were considered to be related to treatment. No clinically relevant changes from baseline to end of study were observed in laboratory measures and vital signs for any group.
CONCLUSIONS: The safety profiles of aclidinium 200 µg and 400 µg were similar in these studies. Long-term treatment with aclidinium was well tolerated in patients with moderate-to-severe COPD.
CLINICAL IMPLICATIONS: Results from these studies demonstrate that twice-daily aclidinium is a well tolerated treatment option for patients with COPD.
DISCLOSURE: James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: Consultant
Stephen Rennard: 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.University of North Carolina, Chapel Hill, NC