One-Year Extension Study of ACCORD COPD I: Safety and Efficacy of Two Doses of Twice-daily Aclidinium Bromide in Patients with COPD

Abstract

This was a 52-week, double-blind, extension study in which COPD patients previously treated with twice-daily (BID) aclidinium bromide 200 μg or 400 μg during a 12-week lead-in study (ACCORD COPD I) continued the same treatment, while patients previously receiving placebo were rerandomized (1:1) to aclidinium 200 μg or 400 μg BID. The primary objective of this study was to evaluate the long-term safety and tolerability of aclidinium treatment. Efficacy outcomes included bronchodilation, health status, and rescue medication use. A total of 467 patients completed the lead-in study and 291 patients consented to participate in the extension. At study end, the percentages of patients who reported a treatment-emergent adverse event (TEAE) were similar for both treatments (200 μg, 77.4%; 400 μg, 73.7%). Incidence of anticholinergic TEAEs was low and similar for both treatments, with dry mouth reported in only 1 patient (400 μg). Cardiac TEAEs were reported by a similarly low percentage of patients (<5% for any event in any group) with no apparent dose dependence. Improvements from baseline in lung function were greatest for patients who received continuous aclidinium treatment and those who were rerandomized from placebo to aclidinium 400 μg; these improvements were generally sustained throughout the study. Health status and overall rescue medication use was improved from baseline for both treatments. The safety profile of twice-daily aclidinium and sustained improvements in lung function and health status throughout the 52-week extension study support its use as a long-term maintenance treatment for patients with COPD. (Clinical trial registration number NCT00970268).

Keywords :

• bronchodilation
• health status
• symptoms
• tolerability

Acknowledgments

The authors would like to thank the investigators and the study team in each of the participating centers.

Declaration of Interest Statement

This work was funded by Forest Research Institute, Inc. (FRI), a wholly owned subsidiary of Forest Laboratories, Inc., and Almirall, S.A. Anthony D’Urzo has received research, consulting and lecturing fees from 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. Edward Kerwin has served on advisory boards or speaker panels for Astra Zeneca, Ironwood, Mylan, Pearl, Pfizer, Sanofi Aventis, Sunovion, and Targacept, has received travel reimbursement from Merck, Forest, and Novartis, and has performed multicenter clinical trials for multiple pharmaceutical companies including Forest and Almirall, S.A. 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. SR has also received honorarium for consulting with the following: 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, 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, Think Equity, UBC, Uptake Medical, Vantage Point Management. Esther Garcia Gil is an employee of Almirall, S.A. Thomas He and Cynthia Caracta are employees of FRI. Editorial assistance by Joy Ramos, PhD, of Prescott Medical Communications Group, Chicago, IL was funded by FRI. There are no other financial disclosures/conflicts of interest.

All the authors were involved in the creation and review of the manuscript, had full access to study data, and take full responsibility for data integrity and accuracy of all data analysis. All authors participated in the writing of this manuscript and are responsible for its content.