General Information

Duaklir Pressair is a combination of aclidinium bromide, an anticholinergic, and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA).

Duaklir Pressair is specifically indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).

Duaklir Pressair is supplied as an inhalation powder, for oral inhalation. The recommended dose of Duaklir Pressair is one oral inhalation of 400 mcg/12 mcg, twice daily (once in the morning and once in the evening). Do not take more than one inhalation twice daily.

Mechanism of Action

Duaklir Pressair is a combination of aclidinium bromide, an anticholinergic, and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA).

Aclidinium bromide is a long-acting antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. The bronchodilation following inhalation of aclidinium bromide is predominantly a site-specific effect.

Formoterol fumarate is a long-acting selective beta2-adrenergic receptor agonist (LABA) (beta2agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator.

Clinical Trial Results

The FDA approval of Duaklir Pressiar was based on a clinical development program that included three dose ranging trials, one active and two placebo-controlled lung function trials of 24 weeks duration; and one 28-week long-term safety extension study. The efficacy of Duaklir was primarily based on one dose ranging trial in 128 subjects with COPD and the three 6-month duration confirmatory trials in 5015 subjects with COPD, including chronic bronchitis and emphysema.

Dose-Ranging Trials

Dose selection for Duaklir Pressair for COPD was primarily based on data for the individual components, aclidinium bromide and formoterol fumarate, in COPD patients.

Aclidinium: Dose selection for aclidinium was supported by a 7-day, randomized, double-blind, active and placebo-controlled, crossover trial evaluating 3 doses of aclidinium bromide(400, 200,and 100 mcg) administered twice daily and an active control in 79 subjects with COPD. A dose ordering was observed, with the aclidinium bromide 400 mcg demonstrating larger improvements in FEV1 over 24 hours compared with aclidinium bromide 200 mcg and 100 mcg. The change from baseline in FEV1 AUC0-12 from placebo after 7 days for the 100, 200, and 400 mcg doses were 154 mL, 176 mL and 208 mL, respectively. The results supported the selection of 400 mcg of aclidinium bromide twice daily in the confirmatory COPD trials.

Formoterol: Dose selection for formoterol was supported by a randomized, double-blind, placebo and active comparator (open-label) controlled, 5-period incomplete unbalanced crossover trial evaluating 3 doses of formoterol fumarate (24, 12, and 6 mcg) administered twice daily and an open-label active comparator in 132 subjects with COPD. The change from baseline in FEV1 AUC0-12 from placebo after 7 days for the 6, 12, and 24 mcg doses were 108 mL, 117 mL, and 162 mL, respectively. The results supported the evaluation of 12 mcg of formoterol twice daily in the confirmatory COPD trials.

Confirmatory Trials

The clinical development program for Duaklir Pressair included two placebo-controlled (Trial 1) and Trial 2 and one active-controlled (Trial 3) randomized, double-blind, parallel-group 24-week trials in subjects with moderate to very severe COPD, including chronic bronchitis and emphysema, designed to evaluate the efficacy of Duaklir Pressair on lung function. The 24-week trials included 4,977 subjects >40 years of age that had a clinical diagnosis of COPD, with a smoking history greater than or equal to 10 pack-years, a post-albuterol FEV1 less than 80% of predicted normal values, and a ratio of FEV1/FVC of less than 0.7. The majority of these patients were male (61%) and Caucasian (94%) with a mean age of 64 years and an average smoking history of 46 pack-years (50% current smokers). Trials 1, 2, and 3 evaluated Duaklir Pressair (aclidinium/formoterol fumarate) 400 mcg/12 mcg, aclidinium 400 mcg, and formoterol fumarate 12 mcg. Trials 1 and 2 included a placebo arm, and Trial 3 included an active, blinded, control arm.
The co-primary endpoints were change from baseline in trough FEV1 and change from baseline in one-hour post-dose FEV1 at Week 24 compared with formoterol fumarate 12 mcg and aclidinium 400 mcg, respectively. In the three trials, Duaklir Pressair demonstrated a statistically significant increase in mean change from baseline in trough FEV1 and change from baseline in one-hour post-dose FEV1 at Week 24 relative to formoterol fumarate 12mcg and aclidinium 400 mcg, respectively.