SESSION TITLE: COPD Safety of Treatment Posters
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PM
PURPOSE: Aclidinium bromide, a long-acting muscarinic antagonist with low systemic exposure due to rapid plasma hydrolysis, is indicated for maintenance treatment of COPD-associated bronchospasm. Muscarinic antagonists are typically associated with anticholinergic adverse events (AEs), and concerns exist regarding their anticholinergic-related cardiovascular (CV) effects. This analysis of 3 studies in moderate to severe COPD patients further examines anticholinergic AEs that may occur with long-term aclidinium treatment.
METHODS: Data were pooled from three phase 3 trials to obtain exposure-adjusted incidence rates for anticholinergic AEs, serious anticholinergic AEs, and related discontinuations. In 2 double-blind 52-week trials, patients were randomized (1:1) to aclidinium 200 µg or 400 µg twice daily (BID); in 1 open-label 40-week trial, solely the 400 µg BID dose was administered. Only data for patients treated with the approved 400 µg BID dose are reported here. Exposure time was defined as total exposure in years, and incidence rates (IRs) were calculated as the number of patients in each category per 1000 patient-years of exposure.
RESULTS: A total of 891 patients in this pooled safety population received aclidinium 400 µg BID, with a total exposure time of 644 patient-years. The highest IRs (per 1000 patient-years; % of patients) of anticholinergic AEs were urinary tract infection (40.4; 2.9%), oropharyngeal pain (24.8; 1.8%), and constipation (20.2; 1.5%). IRs for the 200 µg dose were generally similar to those for the higher dose, indicating a lack of dose dependence. Palpitations (IR, 6.2; 0.4%) was the most common CV-related anticholinergic AE. No serious anticholinergic AEs were reported in ≥0.2% patients on aclidinium 400 µg. The most frequent CV-related anticholinergic AEs leading to discontinuation were palpitations and ventricular tachycardia (IR, 1.6; 0.1% each). No deaths occurred due to anticholinergic AEs in any of these studies.
CONCLUSIONS: These data demonstrate that incidences of anticholinergic AEs are infrequent in patients with COPD receiving long-term aclidinium treatment. These results are consistent with previous data reported in 12- and 24-week placebo-controlled studies.
CLINICAL IMPLICATIONS: Anticholinergic agents have the potential to produce unwanted systemic side effects. These data suggest that long-term aclidinium treatment has a low potential for producing anticholinergic AEs in moderate to severe COPD patients and is thus a valuable maintenance treatment option in these patients.
DISCLOSURE: Anthony D'Urzo: Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline, Sepracor, Schering Plough, Altana, Methapharma, AstraZeneca, ONO pharma, Merck Canada, Forest Laboratories, Novartis Canada/USA, Boehringer Ingelheim (Canada) Ltd, Pfizer Canada, SkyePharma, and KOS Pharmaceuticals Stephen Rennard: Other: Stephen Rennard (SR) has received honoraria for lectures from AARC, Almirall, Am Col Osteopathic Physicians, Asan Medical Center, American Thoracic Society, California Society of Allergy, CME Incite, COPD Foundation, Creative Educational Concepts, Dey, Duke University, Forest, France Foundation, HSC Medical Education, Information TV, Lung Association, Novartis (Horsham, Nycomed, Otsuka, PeerVoice, Pfizer, Shaw Science, University of Washington, University of Alabama Birmingham, VA Sioux Falls., Consultant fee, speaker bureau, advisory committee, etc.: ABIM, Able Associates, Adelphi Research, Align2Acton, Almirall/Prescott, APT Pharma/Britnall, Astra-Zeneca, American Thoracic Society Beilenson, Boehringer Ingelheim, Boehringer Ingelheim (ACCP), BoomCom, Britnall and Nicolini, Capital Research, Chiesi, Clarus Acuity, CommonHealth, Complete Medical Group, Consult Complete, COPDForum, DataMonitor, Decision Resources, Dunn Group, Easton Associates, Equinox, Forest, Frankel Group, Fulcrum, Gerson Lehman, Globe Life Sciences, Consultant fee, speaker bureau, advisory committee, etc.: Guidepoint, Health Advanced, Hoffman LaRoche, Informed, Insyght, KOL Connection, Leerink Swan, M. Pankove, McKinsey, MDRxFinancial, Medimmune, Merck, Novartis, Nycomed, Oriel, Osterman, Peal, Penn Technology, Pennside, Pfizer, PharmaVentures, Pharmaxis, Prescott, Price Waterhouse, Propagate, Pulmonary Reviews, Pulmatrix, Reckner Associates, Recruiting Resource, Roche, Sankyo, Schering, Schlesinger Medical, Scimed, Smith Research, Sudler and Hennessey, Summer Street Research, Talecris, Consultant fee, speaker bureau, advisory committee, etc.: Think Equity, UBC, Uptake Medical, Vantage Point Management Paul Jones: Consultant fee, speaker bureau, advisory committee, etc.: Almirall S.A. Ludmyla Rekeda: Employee: Forest Research Institute Esther Garcia Gil: Employee: Almirall S.A. Cynthia Caracta: Employee: Forest Research Institute
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