SESSION TITLE: COPD LAMA/LABA
SESSION TYPE: Original Investigation Slide
PRESENTED ON: Monday, October 27, 2014 at 01:30 PM - 02:30 PM
PURPOSE: To assess long-term safety and efficacy of aclidinium bromide (AB) in moderate to severe COPD patients.
METHODS: In this open-label, 40-week extension study, patients completing a 12-week double-blind lead-in trial (ACCORD II) were transitioned from randomized treatment (twice-daily [BID] placebo [PBO], AB 200µg, or AB 400µg) to AB 400µg BID. Safety, the primary outcome, was assessed via adverse events (AEs) of new or increased intensity during this extension study. Efficacy parameters included change from baseline (visit 2 lead-in) to week 52 in morning predose (trough) FEV1, peak FEV1, and SGRQ total score. Efficacy was analyzed using an ANCOVA.
RESULTS: Of 454 patients completing the lead-in, 448 continued to the extension. Baseline characteristics (visit 2 lead-in) were similar across sequences, except for unexpected imbalances in FEV1 (1.46L PBO-AB400; 1.40L AB200-AB400; 1.25L AB400-AB400) and in the distribution of severe, stage III COPD (37.4% PBO-AB 400; 45.5% AB200-AB400; 53.1% AB400-AB400). The percentage of patients reporting ≥1 AE was similar across groups; the most common (≥5%) were COPD exacerbation (18.1%) and upper respiratory tract infection (5.8%). Most AEs were mild or moderate, and few were related to treatment (~8% in each sequence): 7.5% PBO-AB400; 8.4% AB200-AB400; and, 8.8% AB400-AB400. Discontinuations due to AEs occurred in 6.8% PBO- AB400, 6.5% AB200-AB200, and 4.8% (AB400-AB400) of patients. Most frequently reported potential anticholinergic events (≥1%) were urinary tract infection (2.5%) and constipation (1.3%), with similar rates across groups. At 52 weeks, changes from baseline in trough FEV1 were 44 mL (PBO-AB400), 29 mL (AB200-AB400) and 48 mL (AB400-AB400). Changes from baseline to week 52 in peak FEV1 were 184mL (PBO-AB400), 176mL (AB200-AB400) and 172mL (AB400-AB400). Changes from baseline to week 52 in SGRQ were -8.25 (PBO-AB400), -6.19 (AB200-AB400) and -6.82 (AB400-AB400) units.
CONCLUSIONS: AB 400µg was well-tolerated over 1 year, with a similar safety profile among treatment sequences. Although unexpected baseline imbalances across groups may have affected the observed treatment benefits of AB, improvements from baseline in efficacy endpoints during the lead-in were generally sustained over 52 weeks.
CLINICAL IMPLICATIONS: Aclidinium 400µg BID is a well-tolerated and effective treatment option for moderate to severe COPD patients. This study was funded by Almirall S.A. and by Forest Research Institute, Inc., a wholly owned subsidiary of Forest Laboratories, Inc.
DISCLOSURE: Stephen Rennard: Other: 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, Align2Action, Almirall, 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 Gary Ferguson: Grant monies (from industry related sources): Forest Research Institute, Consultant fee, speaker bureau, advisory committee, etc.: Forest Research Institute Edward Kerwin: Consultant fee, speaker bureau, advisory committee, etc.: Amphastar, Astra Zeneca, Forest, Ironwood, Merck, Mylan, Novartis, Pearl, Pfizer, Sanofi Aventis, Sunovion, Targacept, Teva and Theravance, Other: Conducted multicenter clinical research trials for approximately seventy pharmaceutical companies Ludmyla Rekeda: Employee: Forest Research Institute Esther Garcia Gil: Employee: Almirall S.A.
No Product/Research Disclosure Information