title: One-Year Safety of Olodaterol Once Daily via Respimat® in Patients with GOLD 2-4 Chronic Obstructive Pulmonary Disease: Results of a Pre-Specified Pooled Analysis.
abstract: The novel long-acting β2-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 μg) QD via Respimat®, formoterol 12 μg twice daily (BID) via Aerolizer® (1222.13 and 1222.14), and placebo for 48 weeks. Patients continued receiving background maintenance therapy, with ∼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 μg, 883 received olodaterol 10 μg, 885 received placebos, and 460 received formoterol 12 μg 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 μg (marketed and registered dose) and 10 μg QD delivered via Respimat® are comparable to placebo and formoterol BID in this population, with no safety signals identified.
authors.affiliation: a Centre for Infection and Immunity , School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast , Belfast , United Kingdom.
authors.forename: Lorcan
authors.initials: L
authors.lastname: McGarvey
authors.affiliation: b Minneapolis VA Health Care System , Minneapolis , Minnesota , USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Niewoehner
authors.affiliation: c McGill University Health Centre , Montreal , Canada.
authors.forename: Sheldon
authors.initials: S
authors.lastname: Magder
authors.affiliation: d Pulmonary Associates of Stamford, Stamford , Connecticut , USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Sachs
authors.affiliation: e Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim , Germany.|f Department of Sports Medicine, Medical Clinic V , University of Tübingen , Tübingen , Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Tetzlaff
authors.affiliation: g Boehringer Ingelheim , Burlington , Ontario , Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Hamilton
authors.affiliation: h Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield , Connecticut , USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Korducki
authors.affiliation: e Boehringer Ingelheim Pharma GmbH & Co. KG , Ingelheim , Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bothner
authors.affiliation: i Department of Medicine, Pulmonary and Critical Care Medicine , University Medical Center Giessen and Marburg, Philipps-Universität Marburg , Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Vogelmeier
authors.affiliation: j Medical Clinic III for Pneumology, Allergology, Sleep and Respiratory Medicine, University Hospital Bochum-Bergmannsheil , Bochum , Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Koch
authors.affiliation: k Pulmonary Research Institute of Southeast Michigan , Livonia , Michigan , USA.
authors.forename: Gary T
authors.initials: GT
authors.lastname: Ferguson
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000368:Aged; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects*; D002423:Cause of Death; D016757:Death, Sudden, Cardiac / Q000453:epidemiology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004334:Drug Administration Schedule; D015716:Electrocardiography, Ambulatory; D005260:Female; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate / Q000008:administration & dosage / Q000009:adverse effects; D006331:Heart Diseases / Q000150:complications / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D020521:Stroke / Q000453:epidemiology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D048588:Benzoxazines; D003692:Delayed-Action Preparations; C549647:olodaterol; D000068759:Formoterol Fumarate
keywords: Mortality Adjudication Committee; bronchodilator; cardiac safety; long-acting β2-agonist