SESSION TITLE: COPD I
SESSION TYPE: Slide Presentations
PRESENTED ON: Sunday, March 23, 2014 at 04:15 PM - 05:15 PM
PURPOSE: With the burden of COPD increasing, new treatment strategies to optimize pharmacotherapy include combination therapies with complementary modes of action. This phase 3 trial evaluated efficacy and safety of fixed-dose combinations of aclidinium, a long-acting anticholinergic indicated for maintenance treatment of COPD-associated bronchospasm, and formoterol, a long-acting β2-agonist, in moderate to severe COPD patients.
METHODS: In this 24-week, double-blind, parallel-group trial, 1692 stable COPD patients (mean prebronchodilator FEV1, 1.36L; mean postbronchodilator FEV1, 53.5% predicted) were randomized (1:1:1:1:1) to twice-daily fixed-dose combination aclidinium 400µg + formoterol 12µg (FDC 400/12), aclidinium 400µg + formoterol 6µg (FDC 400/6), aclidinium 400µg, formoterol 12µg, or placebo (PBO). Coprimary endpoints were change from baseline to Week 24 in 1h morning postdose FEV1 (each FDC vs aclidinium—contribution of formoterol) and morning predose (trough) FEV1 (each FDC vs formoterol—contribution of aclidinium). Adverse events (AEs) were also assessed.
RESULTS: Patients who received FDC 400/12 and 400/6 had significant improvements from baseline over aclidinium in 1h postdose FEV1 at Week 24 (108mL and 87mL, respectively, both p<0.0001). FDC 400/12 provided a significant improvement in trough FEV1 of 45mL vs formoterol 12 (p=0.0102); numerical improvement of 26mL was observed for trough FEV1 with FDC 400/6 over formoterol 12. Overall, more PBO-treated patients discontinued the study (30%) vs other active treatments (range, 18%-22%), but discontinuation rates due to AEs were similar for FDC 400/12 and PBO (6.3% each) and other active treatments (FDC 400/6, 6.6%; aclidinium, 4.7%; formoterol 12, 4.2%). The most common AEs (>5% of patients, any group) were cough (FDC 400/12, 5.1%; FDC 400/6, 3.9%; aclidinium, 2.1%; formoterol 12, 3.0%; PBO, 3.6%) and nasopharyngitis (4.8%, 5.1%, 3.6%, 6.6%, 3.6%, respectively). Percentages of patients with serious AEs were similar for all groups (FDC 400/12, 5.7%; FDC 400/6, 5.4%; aclidinium, 5.0%; formoterol 12, 4.5%; PBO, 3.6%).
CONCLUSIONS: Each aclidinium/formoterol fixed-dose combination improved bronchodilation compared with either monotherapy and was well tolerated, with a similar safety profile to either drug alone or placebo.
CLINICAL IMPLICATIONS: Aclidinium/formoterol 400/12 fixed-dose combination may be a useful treatment option for COPD patients, providing greater bronchodilation than and similar tolerability to either monotherapy or aclidinium/formoterol 400/6.
DISCLOSURE: Anthony D'Urzo: Consultant fee, speaker bureau, advisory committee, etc.: Dr. 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. Stephen Rennard: Consultant fee, speaker bureau, advisory committee, etc.: Stephen Rennard 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.: Stephen Rennard 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, and Forest., Consultant fee, speaker bureau, advisory committee, etc.: (continued) 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, and Schlesinger., Consultant fee, speaker bureau, advisory committee, etc.: (continued) Scimed, Smith Research, Sudler and Hennessey, Summer Street Research, Talecris, Think Equity, UBC, Uptake Medical, Vantage Point Management. Victor Mergel: Employee: Victor Mergel is an employee of Forest Research Institute, Inc. Esther Garcia Gil: Employee: Esther Garcia Gil is an employee of Almirall S.A. Anne Leselbaum: Employee: Anne Leselbaum is an employee of Almirall S.A. Cynthia Caracta: Employee: C. Caracta is an employee of Forest Research Institute, Inc. , Shareholder: C. Caracta 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.