Following administration of single 10, 20, and 244 mcg PERFOROMIST Inhalation Solution doses (calculated on an anhydrous basis) delivered via nebulizer in 12 COPD patients, on average, about 1.1% to 1.7% of the dose was excreted in the urine as unchanged formoterol as compared to about 3.4% excreted unchanged following inhalation administration of 12 mcg of formoterol fumarate dry powder. Renal clearance of formoterol following inhalation administration of PERFOROMIST Inhalation Solution in these subjects was about 157 mL/min. Based on plasma concentrations measured following the 244 mcg dose, the mean terminal elimination half-life was determined to be 7 hours.

Gender

As reported for another formoterol fumarate inhalation formulation, upon correction for body weight, pharmacokinetics of formoterol fumarate did not differ significantly between males and females.

Geriatric, Pediatric, Hepatic/Renal Impairment

The pharmacokinetics of formoterol fumarate has not been studied in elderly and pediatric patient populations. The pharmacokinetics of formoterol fumarate has not been studied in subjects with hepatic or renal impairment.

Animal Pharmacology

Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown. [See DRUG INTERACTIONS, Xanthine Derivatives, Steroids, or Diuretics]

Clinical Studies

Adult COPD Trial

PERFOROMIST (formoterol fumarate) Inhalation Solution was evaluated in a 12-week, double-blind, placebo- and active-controlled, randomized, parallel-group, multicenter trial conducted in the United States. Of a total enrollment of 351 adults (age range: 40 to 86 years; mean age: 63 years) with COPD who had a mean pre-bronchodilator FEV₁ of 1.34 liters (44% of predicted), 237 patients were randomized to PERFOROMIST Inhalation Solution 20 mcg or placebo, administered twice daily via a PARI-LC Plus® nebulizer with a PRONEB® Ultra compressor. The diagnosis of COPD was based upon a prior clinical diagnosis of COPD, a smoking history (at least 10 pack-years), age (at least 40 years), and spirometry results (pre-bronchodilator baseline FEV₁ at least 30% and less than 70% of the predicted value, and the FEV₁/FVC less than 70%). About 58% of patients had bronchodilator reversibility, defined as a 10% or greater increase in FEV₁ after inhalation of 2 actuations (180 mcg) of albuterol from a metered dose inhaler. About 86% (106) of patients treated with PERFOROMIST Inhalation Solution and 74% (84) of placebo patients completed the trial.

PERFOROMIST Inhalation Solution 20 mcg twice daily resulted in significantly greater post-dose bronchodilation (as measured by serial FEV₁ for 12 hours post-dose; the primary efficacy analysis compared to placebo when evaluated at endpoint (week 12 for completers and last observation for dropouts). Similar results were seen on Day 1 and at subsequent timepoints during the trial.

Mean FEV₁ measurements at Day 1 (Figure 1) and at endpoint (Figure 2) are shown below.

Figure 1
Mean* FEV₁ at Day 1

Figure 2
Mean* FEV₁ at Endpoint after 12 Weeks of Treatment

*Figures show least-squares means adjusted for baseline FEV₁

Patients treated with PERFOROMIST Inhalation Solution used less rescue albuterol during the trial compared to patients treated with placebo.

Examination of age (≥65 or younger) and gender subgroups did not identify differences in response to PERFOROMIST Inhalation Solution. There were too few non-Caucasian subjects to assess differences in populations defined by race adequately.

In the 12 week study, 78% of subjects achieved a 15% increase from baseline FEV₁ following the first dose of PERFOROMIST Inhalation Solution 20 mcg. In these subjects, the median time to onset of bronchodilation, defined as 15% increase in FEV₁, was 11.7 minutes. When defined as an increase in FEV₁ of 12% and 200 mL, the time to onset of bronchodilation was 13.1 minutes after dosing. The median time to peak bronchodilator effect was 2 hours after dosing.

Bookmark this page: