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ACCORD COPD II: A Randomized Clinical Trial to Evaluate the 12-Week Efficacy and Safety of Twice-Daily Aclidinium Bromide in Chronic Obstructive Pulmonary Disease Patients

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Abstract

Background and Objectives

Aclidinium bromide is a long-acting muscarinic antagonist approved for the long-term maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD). This 12-week phase III study evaluated efficacy and tolerability of aclidinium 200 or 400 μg in patients with moderate-to-severe COPD.

Methods

In this double-blind study, 544 patients with COPD were randomized to placebo or twice-daily aclidinium 200 or 400 μg administered by Genuair®/Pressair®. Lung function, health status [measured by the St. George’s Respiratory Questionnaire (SGRQ)], dyspnea [measured using the Transition Dyspnea Index (TDI)], and safety were assessed throughout the study.

Results

Mean changes from baseline in morning trough forced expiratory volume in 1 s (FEV1) at week 12 (primary endpoint) were significantly higher for aclidinium than for placebo (200 μg, 51 mL; 400 μg, 72 mL; both p < 0.05). Aclidinium also significantly improved other lung function outcomes. At week 12, improvements from baseline were observed with aclidinium in SGRQ total score (200 μg, −6.0; 400 μg, −5.4) and TDI focal score (200 μg, 1.0; 400 μg, 1.3). Furthermore, clinically important improvements in SGRQ total and TDI focal scores were achieved by 45 and 51 % of patients, respectively, who received aclidinium 400 μg, with a significant difference versus placebo for TDI (p < 0.05). Anticholinergic-related adverse events (e.g., dry mouth) were infrequent, occurring <2 % for any event in any treatment group. Both aclidinium doses were well tolerated.

Conclusion

This study demonstrates efficacy and safety of aclidinium in COPD patients. Unexpected baseline imbalances between treatment groups may have impacted the aclidinium treatment benefit in this study.

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Notes

  1. Registered trademarks of Almirall, SA, Barcelona, Spain for use within the European Union, Iceland, Norway, and Switzerland as Genuair® and within the USA as Pressair® .

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Acknowledgments

The authors would like to thank the ACCORD II study investigators. The authors would also like to thank Gary Koch, PhD and Paul Jones, PhD, FRCP for helpful discussions. Editorial assistance by Joy Ramos, PhD of Prescott Medical Communications Group (Chicago, IL, USA) was funded by Forest Research Institute (FRI).

Funding

This study was funded by FRI, a wholly owned subsidiary of Forest Laboratories, Inc., and Almirall, S.A.

Author Contributions

Stephen I. Rennard, Paul D. Scanlon, Gary T. Ferguson, and Ludmyla Rekeda contributed to the analysis and interpretation of data, critically revised the manuscript for important intellectual content, and provided final approval of the manuscript. Brian T. Maurer, Esther Garcia Gil, and Cynthia F. Caracta contributed to the design of the study and analysis and interpretation of data, critically revised the manuscript for important intellectual content, and provided final approval of the manuscript.

Disclosures

Stephen I. 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. Stephen I. Rennard has also received honoraria for consulting with the following: 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. Paul D. Scanlon has conducted research for Boehringer Ingelheim, Forest Laboratories, Inc., GlaxoSmithKline, Pearl Therapeutics, Pfizer Inc., and Novartis and has served on scientific advisory committees for GlaxoSmithKline and Merck. Gary T. Ferguson has provided consulting services, participated in advisory boards, served as speaker, and conducted research for various pharmaceutical companies including Forest Laboratories, Inc., GlaxoSmith Kline, Boehringer Ingelheim, AstraZeneca, Pearl Therapeutics, Sunovion, and Novartis. Ludmyla Rekeda, Brian T. Maurer, and Cynthia F. Caracta are employees of FRI. Esther Garcia Gil is an employee of Almirall, SA.

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Authors and Affiliations

  1. Division of Pulmonary, Critical Care, Sleep and Allergy, 985910 Nebraska Medical Center, Omaha, NE, 68198-5910, USA

    Stephen I. Rennard

  2. Mayo Clinic, Rochester, MN, USA

    Paul D. Scanlon

  3. Pulmonary Research Institute of Southeast Michigan, Livonia, MI, USA

    Gary T. Ferguson

  4. Forest Research Institute, Inc., Jersey City, NJ, USA

    Ludmyla Rekeda, Brian T. Maurer & Cynthia F. Caracta

  5. Almirall, S. A., Barcelona, Spain

    Esther Garcia Gil

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  1. Stephen I. Rennard
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  7. Cynthia F. Caracta
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Corresponding author

Correspondence to Stephen I. Rennard.

Additional information

Trial registration: ClinicalTrials.gov identifier: NCT01045161.

On behalf of the ACCORD COPD II Study Investigators.

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Rennard, S.I., Scanlon, P.D., Ferguson, G.T. et al. ACCORD COPD II: A Randomized Clinical Trial to Evaluate the 12-Week Efficacy and Safety of Twice-Daily Aclidinium Bromide in Chronic Obstructive Pulmonary Disease Patients. Clin Drug Investig 33, 893–904 (2013). https://doi.org/10.1007/s40261-013-0138-1

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