TORONTO – No long-term safety signals were seen in a randomized trial that tested the formoterol fumarate inhalation solution (Perforomist, Mylan) against placebo in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Safety was confirmed despite patients being permitted to remain on other background treatment for COPD, including inhaled corticosteroids and anticholinergics, in this study presented at the CHEST annual meeting. An additional benefit of the therapy was that it significantly improved lung function from baseline, according to some spirometry measures.
The Food and Drug Administration approved , a long-acting beta-2 agonist (LABA), as a nebulized maintenance treatment for bronchoconstriction in COPD. Because of a concern about long-term LABA safety in asthma patients, said Dr. Hanania, the FDA mandated this 1-year phase 4 study to evaluate the long-term safety of formoterol in patients with moderate to severe COPD.
This multicenter, double-blind, noninferiority study randomly assigned 1,071 patients with moderate to severe COPD (mean FEV1, 44.4% of predicted value, at least one exacerbation in the past 12 months) to receive either nebulized formoterol 20 mcg/2 mL twice daily or matching placebo for up to 12 months. Subjects were permitted to remain on stable COPD therapy, including inhaled corticosteroids and anticholinergics but excluding long-acting beta-agonists.
Formoterol was noninferior to placebo for the primary safety endpoint, defined as a first occurrence of respiratory-related death, COPD-related emergency department visit, or COPD-related hospitalization, with an estimated hazard ratio of 0.965.
Formoterol significantly improved trough forced expiratory volume in 1 second (FEV1), compared with placebo at 3 and 6 months of treatment, with (least squares) mean estimated differences of 42 mL (P = .007) and 41 mL (P = .025), respectively, but not at 9 or 12 months. Forced vital capacity was significantly improved with formoterol over placebo at all study visits (3, 6, 9, and 12 months), but improvements from baseline in inspiratory capacity did not significantly differ from placebo.
Mean age of study patients was 62.6 years and 48.5% were female. At baseline, about half of patients were still smokers, half were on inhaled corticosteroids, and about one-third were on concomitant long-acting muscarinic antagonists, mainly , reported Dr. Hanania. The vast majority of patients had moderate or severe COPD, with less than 1% having very severe disease at baseline.
In response to a question on dosing, Dr. Hanania told attendees, “One thing we have to keep in mind is that formoterol is a full agonist, so there are dose-dependent adverse effects. So, even though you get better lung function as you go up on the dose, there’s no free lunch and always the potential for adverse effects.”
The safety data was previously presented at the American Thoracic Society meeting in May 2017 (Hanania N et al. [abstract]), while the lung function data are new, said Dr. Hanania.
Dr. Hanania reported being an adviser for several pharmaceutical companies, including Mylan. Four of the six authors of the study’s abstract are employees of Mylan.