General Information

Tudorza Pressair (aclidinium bromide inhalation powder) consists of a dry powder formulation of aclidinium bromide for oral inhalation only. Aclidinium bromide is an anticholinergic with specificity for muscarinic receptors.

Tudorza Pressair is specifically indicated for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

Mechanism of Action

Tudorza Pressair (aclidinium bromide inhalation powder) consists of a dry powder formulation of aclidinium bromide for oral inhalation only. Aclidinium bromide is an anticholinergic with specificity for muscarinic receptors. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptor at the smooth muscle leading to bronchodilation.

Side Effects

Adverse events associated with the use of Tudorza Pressair may include, but are not limited to, the following:

• headache
• nasopharyngitis
• cough

Dosing/Administration

Tudorza Pressair is a breath-actuated, multi-dose dry powder inhaler metering 400 mcg of aclidinium bromide per actuation. The recommended dose of Tudorza Pressair is one oral inhalation of 400 mcg, twice daily.

Clinical Trial Results

The FDA approval of Tudorza Pressair was based on a dose-ranging trial (Trial A) for nominal dose selection and three confirmatory trials (Trials B, C and D).
Dose-ranging trial (Trial A)
This randomized, double-blind, placebo-controlled, active-controlled, crossover trial included seven-day treatment periods separated by five-day washout periods. The trial enrolled 79 subjects who had a clinical diagnosis of COPD, were 40 years of age or older, had a history of smoking at least 10 pack-years, had a forced expiratory volume in one second (FEV1) of at least 30 percent and less than 80 percent of predicted normal value, and a ratio of FEV1 over forced vital capacity (FEV1/FVC) of less than 0.7. The subjects received Tudorza Pressair doses of 400 mcg, 200 mcg and 100 mcg twice daily, formoterol active control and placebo. The effect on trough FEV1 and serial FEV1 in subjects treated with the Tudorza Pressair 100 mcg and 200 mcg twice daily doses was lower compared to subjects treated with the Tudorza Pressair 400 mcg twice daily dose.
Confirmatory trials (Trials B, C and D)
These randomized, double-blind, placebo-controlled trials enrolled 1,276 subjects who had a clinical diagnosis of COPD, were 40 years of age or older, had a history of smoking at least 10 pack-years, had an FEV1 of at least 30 percent and less than 80 percent of predicted normal value, and a ratio of FEV1/FVC of less than 0.7. The subjects received Tudorza Pressair 400 mcg twice daily (n=636) and placebo (n=640). Trials B and C were three months in duration, and trial D was six months in duration. Tudorza Pressair 400 mcg resulted in statistically significantly greater bronchodilation as measured by change from baseline in morning pre-dose FEV1 at 12 weeks (the primary efficacy endpoint) compared to placebo in all three trials.