Long-term safety of nebulized formoterol: Results of a twelve-month open-label clinical trial

Abstract

Formoterol fumarate is a long-acting β2-agonist that is an effective bronchodilator for the maintenance management of patients with chronic obstructive pulmonary disease. The safety profile of the newly developed nebulized formoterol was evaluated over a twelve-month period in an open-label, active-control study. After completing a twelve-week double-blind double-dummy period, 569 subjects with chronic obstructive pulmonary disease entered an open-label extension study and received twice-daily 20 µg formoterol fumarate inhalation solution for nebulization (FFIS) or 12 µg formoterol fumarate dry powder inhalation (FA) for 52 weeks. Most of the FFIS-treated subjects (86%) completed at least six months of open-label treatment with over 90% compliance, comparable to the FA group (88%). Results of safety monitoring for adverse events, laboratory values, and cardiac changes were similar between treatment groups. Three hundred forty (73%) of FFIS-treated subjects and 83 (78%) of FA-treated subjects experienced an adverse event over the course of the study, the majority of which were mild to moderate and considered unrelated to treatment. COPD exacerbation occurred in 15.8% of FFIS-treated and 17.9% of FA-treated subjects. Deaths, serious adverse events, and discontinuations for adverse events occurred in 1.3, 16.2, and 5.4% of the nebulized group versus 1.9, 17.9, and 7.5% of the inhaled group, respectively. There were no clinically important changes from baseline in laboratory tests, including serum potassium and glucose, or vital signs and no treatment-related increases in cardiac arrhythmias, heart rate, or QTc prolongation. We conclude that nebulized formoterol fumarate twice daily is well tolerated over long-term treatment in moderate-to-severe COPD subjects and has a similar safety profile to the DPI formulation.