In a clinical study in 19 adult patients with mild asthma, the bronchoprotective effect of formoterol, as assessed by methacholine challenge, was studied following an initial dose of 24 mcg (twice the recommended dose) and after 2 weeks of 24 mcg twice daily. Tolerance to the bronchoprotective effects of formoterol was observed as evidenced by a diminished bronchoprotective effect on FEV₁ after 2 weeks of dosing, with loss of protection at the end of the 12 hour dosing period.

Rebound bronchial hyper-responsiveness after cessation of chronic formoterol therapy has not been observed.

In three large clinical trials in patients with asthma, while efficacy of formoterol versus placebo was maintained, a slightly reduced bronchodilatory response (as measured by 12-hour FEV₁ AUC) was observed within the formoterol arms over time, particularly with the 24 mcg twice daily dose (twice the daily recommended dose). A similarly reduced FEV₁ AUC over time was also noted in the albuterol treatment arms (180 mcg four times daily by metered-dose inhaler).

Clinical Trials

Adolescent and Adult Asthma Trials

In a placebo-controlled, single-dose clinical trial, the onset of bronchodilation (defined as a 15% or greater increase from baseline in FEV₁) was similar for FORADIL AEROLIZER and albuterol 180 mcg by metered-dose inhaler.

In single-dose and multiple-dose clinical trials, the maximum improvement in FEV₁ for FORADIL AEROLIZER 12 mcg generally occurred within 1 to 3 hours, and an increase in FEV₁ above baseline was observed for 12 hours in most patients.

FORADIL AEROLIZER 12 mcg twice daily was compared to FORADIL AEROLIZER 24 mcg twice daily, albuterol 180 mcg four times daily by metered-dose inhaler, and placebo in a total of 1095 adult and adolescent patients 12 years of age and above with mild-to-moderate asthma (defined as FEV₁ 40%-80% of the patient's predicted normal value) who participated in two pivotal, 12-week, multi-center, randomized, double-blind, parallel group studies.

The results of both studies showed that FORADIL AEROLIZER 12 mcg twice daily resulted in significantly greater post-dose bronchodilation (as measured by serial FEV₁ for 12 hours post-dose) throughout the 12-week treatment period. There was no significant difference in post-dose bronchodilation between FORADIL AEROLIZER 12 mcg twice daily and FORADIL AEROLIZER 24 mcg twice daily, but serious asthma exacerbations occurred more commonly in the higher dose group (see WARNINGS and ADVERSE REACTIONS). Mean FEV₁ measurements from both studies are shown below for the first and last treat-met days (see Figures 1 and 2).

Figures 1a and 1b: Mean FEV₁ from Clinical Trial A

Figures 2a and 2b: Mean FEV₁ from Clinical Trial B

Compared with placebo and albuterol, patients treated with FORADIL AEROLIZER 12 mcg demonstrated improvement in many secondary efficacy endpoints, including improved combined and nocturnal asthma symptom scores, fewer nighttime awakenings, fewer nights in which patients used rescue medication, and higher morning and evening peak flow rates. FORADIL AEROLIZER 24 mcg twice daily did not provide any additional improvements in these secondary endpoints compared to FORADIL AEROLIZER 12 mcg twice daily.

A 16-week, randomized, multi-center, double-blind, parallel-group study enrolled 1568 patients 12 years of age and older with mild-to-moderate asthma (defined as FEV₁ ≥ 40% of the patient's predicted normal value) in three treatment groups:FORADIL AEROLIZER 12 mcg twice daily, FORADIL AEROLIZER 24 mcg twice daily, and placebo. The study's primary endpoint was the incidence of serious asthma-related adverse events. Serious asthma exacerbations occurred in 3 (0. 6%) patients who received FORADIL AEROLIZER 12 mcg twice daily, 2 (0. 4%) patients who received FORADIL AEROLIZER 24 mcg twice daily, and 1 (0. 2%) patient who received placebo. The size of this study was not adequate to precisely quantify the differences in serious asthma exacerbation rates between treatment groups. All serious asthma exacerbations resulted in hospitalizations. While there were no deaths in the study, the duration and size of this study were not adequate to quantify the rate of asthma-related death. See WARNINGS for information about a study which compared another long-acting beta₂-adrenergic agonist to placebo.

Pediatric Asthma Trial

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