Long-term Safety of a Fixed-Dose Combination of Aclidinium Bromide/Formoterol Fumarate in Patients With Stable Moderate to Severe COPD

Abstract

SESSION TITLE: COPD PostersSESSION TYPE: Poster PresentationsPRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PMPURPOSE: Treatment guidelines for chronic obstructive pulmonary disease (COPD) recommend combination therapy of 2 or more long-acting bronchodilators with different mechanisms of action. Here we report the long-term safety of a fixed-dose combination of aclidinium bromide, a long-acting muscarinic antagonist indicated for maintenance treatment of COPD-associated bronchospasm, with formoterol fumarate, a long-acting β2-agonist, in patients with COPD.METHODS: In this phase 3, double-blind, parallel-group, active-controlled study, patients with moderate to severe COPD were randomized 2:1 to twice-daily (BID) aclidinium 400 µg/formoterol 12 µg (FDC 400/12) or formoterol 12 µg alone for 52 weeks, both administered via a multidose dry powder inhaler (Genuair®/Pressair®). Safety and tolerability were assessed via adverse events (AEs).RESULTS: A total of 590 patients were randomized, all of whom were included in the safety population. In this study (FDC 400/12, n=392; formoterol, n=198), patients had a mean baseline forced expiratory volume in 1 second (FEV1) of 1.3 L and postbronchodilator FEV1 % predicted of 51.3%. A similar percentage of patients who received FDC 400/12 or formoterol completed the study (67.6% and 67.2%, respectively), with AEs leading to study discontinuation reported by similar proportions of patients (6.6% and 7.1%, respectively). AEs were reported by 280 (71.4%) and 130 (65.7%) patients in the FDC 400/12 and formoterol groups, respectively. The most commonly reported AEs (ie, ≥5% in both FDC 400/12 and formoterol) were urinary tract infection (6.6% and 5.6%, respectively) and sinusitis (5.1% and 5.6%, respectively). Serious AEs (SAEs) were reported by a similar proportion of patients treated with FDC 400/12 (n=38 [9.7%]) or formoterol (n=21 [10.6%]). Pneumonia was the most frequently reported SAE, occurring in 4 patients (1.0%) and 1 patient (0.5%) in the FDC 400/12 and formoterol groups, respectively. On-therapy deaths occurred in 5 (1.3%) patients with FDC 400/12 (sudden cardiac death etiology unknown, n=2; suicide, metastatic lung cancer, cardiopulmonary arrest, n=1 each) and 1 (0.5%) patient with formoterol (COPD exacerbation).CONCLUSIONS: Long-term treatment with a twice-daily fixed-dose combination of aclidinium/formoterol was well tolerated in patients with COPD, with an AE profile generally similar to that of formoterol alone.CLINICAL IMPLICATIONS: Aclidinium/formoterol fixed-dose combination may be a safe therapeutic option in patients with moderate to severe COPD.DISCLOSURE: Barry Make: Consultant fee, speaker bureau, advisory committee, etc.: Barry Make received payment for service on the advisory boards of Forest Pharmaceuticals, AstraZeneca, Novartis, Merck, Boehringer Ingelheim, Pfizer, Ikaria, and GlaxoSmithKline, consulting fees from Astellas Pharma, and Talecris Biotherapeutics, lecture fees from GlaxoSmithKline, Boehringer Ingelheim, Pfizer, and Forest Pharmaceuticals, payment for video presentation preparation from Boehringer Ingelheim and Pfizer, payment for document reviews from Spiration., Grant monies (from industry related sources): Barry Make received grant support from AstraZeneca, GlaxoSmithKline, Pfizer, Nabi Biopharmaceuticals, Boehringer Ingelheim, Forest, and Sunovion, Grant monies (from sources other than industry): Barry Make received grant support from the National Heart Lung, and Blood Institute, James Donohue: Consultant fee, speaker bureau, advisory committee, etc.: Dr. Donohue has received consultant/speaker/advisory fees from Novartis, GlaxoSmithKline, Boehringer-Ingelheim, Forest and Pfizer Xiaoyun Zhong: Employee: X. Zhong is an employee of Forest Research Institute, Inc. Anne Leselbaum: Employee: Anne Leselbaum is an employee of Almirall S.A. Cynthia Caracta: Employee: Cynthia Caracta is an employee of Forest Research Institute, Inc., Shareholder: Cynthia Caracta is is a stockowner and has received stock options from Forest Laboratories, Inc.Aclidinium bromide (Tudorzo/Pressair, Eklira/Genuair, Breo/Ellipta) is approved for the maintenance treatment of COPD-associated bronchspasm. The fixed-dose combination of aclidinium bromide/formoterol fumarate is being developed, but not yet approved, for its commercial use for the treatment of COPD.