Phase 4 Study of Formoterol Fumarate Finds Safety Outcomes Similar to Placebo

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A phase 4 study of formoterol fumarate showed similar safety performance as placebo in patients with moderate-to-severe chronic obstructive pulmonary disease, according to a recently published study.

A phase 4 study of formoterol fumarate (Perforomist), a long-acting β2-agonist (LABA), was shown to be noninferior to placebo in regard to safety in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD), according to a recently published study.

In addition, fewer treatment withdrawals and larger lung function improvements were observed with formoterol fumarate compared with placebo when added to other maintenance COPD therapies.

The authors said the FDA requested the phase 4, or postmarketing commitment, study to evaluate long-term safety in patients with COPD.

The multicenter, randomized, double-blind, placebo-controlled, noninferiority study included 1071 patients with moderate-to-severe COPD on stable COPD therapy, who received either formoterol fumarate (20 mcg; n = 541) or placebo (n = 530) twice daily.

The mean age of the cohort was 62.6 years; 48.5% were male and nearly 90% were white.


The primary end point was the combined incidence of respiratory death, first COPD-related emergency department (ED) visit, or first COPD exacerbation-related hospitalization in the following year.

Noninferiority to placebo was concluded if the 2-sided 90% CI of the hazard ratio (HR) of formoterol fumarate to placebo was less than 1.5. Secondary end points included spirometry.

The planned 1-year treatment period was completed by 520 patients; 551 discontinued prematurely (formoterol fumarate, 45.7%; placebo, 57.4%).

The median treatment duration was approximately 10 and 7 months for formoterol fumarate and placebo, respectively.

Among 1071 randomized patients, 121 had at least 1 primary event (formoterol fumarate, 11.8%; placebo,: 10.8%). The estimated HR of a primary event with formoterol fumarate versus placebo was 0.965 (90% CI, 0.711-1.308), demonstrating that formoterol fumarate was noninferior to placebo, the authors said.

No respiratory deaths were observed in the formoterol fumarate group. Adverse events were similar for formoterol fumarate versus placebo (patients with ≥1 treatment-emergent adverse event: 374 [69.1%] vs 369 [69.6%], respectively).

Compared with placebo, formoterol fumarate demonstrated statistically greater improvements from baseline in trough forced expiratory volume in 1 second (FEV1), forced vital capacity, percent predicted FEV1, and patient-reported outcomes.

The authors said that treatment for 1 year with formoterol fumarate delivered by twice-daily nebulization in patients with moderate-to-severe COPD is not associated with an increase in the combined incidence of respiratory death, COPD-related ED visits, or COPD exacerbation-related hospitalizations compared with placebo.

In general, safety outcomes were similar between formoterol fumarate and placebo groups, and drug-related life-threatening respiratory or cardiac events were not observed.

Secondary end points demonstrated a numerically lower probability of COPD-related ED visits or COPD-related hospitalizations with formoterol fumarate versus placebo.

Although the study was not designed to evaluate efficacy, greater improvement in lung function, quality of life, dyspnea, and lower rescue medication use were observed with formoterol fumarate compared with placebo, despite patients being permitted to remain on other background treatments for COPD.


Hanania NA, Sethi S, Koltun A, Ward JK, Spanton J, Ng D. Long-term safety and efficacy of formoterol fumarate inhalation solution in patients with moderate-to-severe COPD. [published online December 27, 2019]. Int J Chron Obstruct Pulmon Dis. doi: 10.2147/COPD.S173595.