PMID- 25692310 OWN - NLM STAT- MEDLINE DCOM- 20160720 LR - 20231111 IS - 1541-2563 (Electronic) IS - 1541-2555 (Print) IS - 1541-2563 (Linking) VI - 12 IP - 5 DP - 2015 TI - One-Year Safety of Olodaterol Once Daily via Respimat(R) in Patients with GOLD 2-4 Chronic Obstructive Pulmonary Disease: Results of a Pre-Specified Pooled Analysis. PG - 484-93 LID - 10.3109/15412555.2014.991864 [doi] AB - The novel long-acting beta2-agonist olodaterol demonstrated an acceptable safety profile in short-term phase II clinical studies. This analysis of four randomized, double-blind, placebo-controlled, parallel-group, phase III studies (1222.11, NCT00782210; 1222.12, NCT00782509; 1222.13, NCT00793624; 1222.14, NCT00796653) evaluated the long-term safety of olodaterol once daily (QD) in a large cohort of patients with moderate to very severe (Global initiative for chronic Obstructive Lung Disease 2-4) chronic obstructive pulmonary disease (COPD). The studies compared olodaterol (5 or 10 mug) QD via Respimat(R), formoterol 12 mug twice daily (BID) via Aerolizer(R) (1222.13 and 1222.14), and placebo for 48 weeks. Patients continued receiving background maintenance therapy, with approximately 60% receiving concomitant cardiovascular therapy and 25% having a history of concomitant cardiac disease. Pre-specified analyses of pooled data assessed the adverse events (AEs) and serious AEs in the whole population, and in subgroups with cardiac disease, along with in-depth electrocardiogram and Holter monitoring. In total, 3104 patients were included in the safety analysis: 876 received olodaterol 5 mug, 883 received olodaterol 10 mug, 885 received placebos, and 460 received formoterol 12 mug BID. Overall incidence of on-treatment AEs (71.2%), serious AEs (16.1%), and deaths (1.7%) were balanced across treatment groups. Respiratory and cardiovascular AEs, including major adverse cardiac events, were reported at similar frequencies in placebo and active treatment groups. The safety profiles of both olodaterol 5 mug (marketed and registered dose) and 10 mug QD delivered via Respimat(R) are comparable to placebo and formoterol BID in this population, with no safety signals identified. FAU - McGarvey, Lorcan AU - McGarvey L AD - a Centre for Infection and Immunity , School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast , Belfast , United Kingdom. FAU - Niewoehner, Dennis AU - Niewoehner D AD - b Minneapolis VA Health Care System , Minneapolis , Minnesota , USA. FAU - Magder, Sheldon AU - Magder S AD - c McGill University Health Centre , Montreal , Canada. FAU - Sachs, Paul AU - Sachs P AD - d Pulmonary Associates of Stamford, Stamford , Connecticut , USA. FAU - Tetzlaff, Kay AU - Tetzlaff K AD - e Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim , Germany. AD - f Department of Sports Medicine, Medical Clinic V , University of Tubingen , Tubingen , Germany. FAU - Hamilton, Alan AU - Hamilton A AD - g Boehringer Ingelheim , Burlington , Ontario , Canada. FAU - Korducki, Lawrence AU - Korducki L AD - h Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield , Connecticut , USA. FAU - Bothner, Ulrich AU - Bothner U AD - e Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim , Germany. FAU - Vogelmeier, Claus AU - Vogelmeier C AD - i Department of Medicine, Pulmonary and Critical Care Medicine , University Medical Center Giessen and Marburg, Philipps-Universitat Marburg , Germany. FAU - Koch, Andrea AU - Koch A AD - j Medical Clinic III for Pneumology, Allergology, Sleep and Respiratory Medicine, University Hospital Bochum-Bergmannsheil , Bochum , Germany. FAU - Ferguson, Gary T AU - Ferguson GT AD - k Pulmonary Research Institute of Southeast Michigan , Livonia , Michigan , USA. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20150218 PL - England TA - COPD JT - COPD JID - 101211769 RN - 0 (Adrenergic beta-2 Receptor Agonists) RN - 0 (Benzoxazines) RN - 0 (Delayed-Action Preparations) RN - VD2YSN1AFD (olodaterol) RN - W34SHF8J2K (Formoterol Fumarate) SB - IM MH - Adrenergic beta-2 Receptor Agonists/administration & dosage/*adverse effects MH - Aged MH - Benzoxazines/administration & dosage/*adverse effects MH - Cause of Death MH - Death, Sudden, Cardiac/epidemiology MH - Delayed-Action Preparations/administration & dosage/adverse effects MH - Disease Progression MH - Drug Administration Schedule MH - Electrocardiography, Ambulatory MH - Female MH - Forced Expiratory Volume MH - Formoterol Fumarate/administration & dosage/adverse effects MH - Heart Diseases/complications/drug therapy MH - Humans MH - Hypertension/complications/drug therapy MH - Male MH - Metered Dose Inhalers MH - Middle Aged MH - Myocardial Infarction/epidemiology MH - Pulmonary Disease, Chronic Obstructive/complications/*drug therapy/mortality MH - Stroke/epidemiology PMC - PMC4778540 OTO - NOTNLM OT - Mortality Adjudication Committee OT - bronchodilator OT - cardiac safety OT - long-acting beta2-agonist EDAT- 2015/02/19 06:00 MHDA- 2016/07/21 06:00 PMCR- 2016/03/04 CRDT- 2015/02/19 06:00 PHST- 2015/02/19 06:00 [entrez] PHST- 2015/02/19 06:00 [pubmed] PHST- 2016/07/21 06:00 [medline] PHST- 2016/03/04 00:00 [pmc-release] AID - 991864 [pii] AID - 10.3109/15412555.2014.991864 [doi] PST - ppublish SO - COPD. 2015;12(5):484-93. doi: 10.3109/15412555.2014.991864. Epub 2015 Feb 18.