PURPOSE: Formoterol is a long-acting selective β2-agonist with a rapid onset and history of safety and efficacy in the treatment of respiratory disease. Formoterol fumarate inhalation solution (FFIS) has been developed for maintenance treatment of COPD. The long-term safety of FFIS was compared to formoterol fumarate (FA) delivered by dry powder inhalation (DPI) over a 12-month period.
METHODS: This was a 52-week open-label extension study, which followed a 12-week randomized, double-blind, placebo- and active-controlled study. Subjects with moderate-to-severe COPD and no significant comorbidities received either 20 mcg nebulized FFIS or 12 mcg FA by DPI twice daily for one year. Safety evaluations included adverse event (AE) monitoring, 12-lead ECGs, clinical laboratory results, vital signs, and physical examinations.
RESULTS: 569 subjects were enrolled (mean age 64 yrs, 53% male), and over 85% completed ≥6 months treatment with >90% compliance. Approximately 74% of subjects experienced an AE, the most common of which was COPD exacerbation (16% FFIS, 18% FA). The incidence of AEs, serious AEs and discontinuations for AEs was similar between the FFIS and FA groups. ECG results were similar with no treatment-related increases in cardiac arrhythmias, heart rate, or QTc prolongation. There were no clinically important changes from baseline in laboratory tests, including serum potassium and glucose, vital signs, or physical examinations. Changes from baseline to Week 52 for glucose and potassium were +0.4 mg/dL and 0.0 mEq/L, respectively, in the FFIS group.
CONCLUSION: Twice daily nebulized formoterol was well tolerated over 12 months of treatment in subjects with moderate-to-severe COPD. Results from this open-label safety study indicate FFIS is a safe option for long-term maintenance therapy of bronchoconstriction associated with COPD.
CLINICAL IMPLICATIONS: Nebulized delivery of formoterol provides a safe treatment alternative for COPD patients who prefer or require nebulization. Twice daily nebulized formoterol provides an effective and well-tolerated long-term maintenance treatment for COPD.
DISCLOSURE: Sammy Campbell, No Product/Research Disclosure Information; Grant monies (from industry related sources) Sammy Campbell: Grant monies (non-industry): none Grant monies (industry): Astra-Zeneca, Novartis; Employee Kimberly Denis-Mize and Mike Rinehart are employees of Dey, LP, Sammy Campbell: Employee-University of Arizona (only); Consultant fee, speaker bureau, advisory committee, etc. Sammy Campbell: Consultant, speaker bureau, advisory committee: Schering, Sepracor, Pfizer, Boehringer-Ingelheim