General Information

Incruse Ellipta (umeclidinium inhalation powder) is a long-acting muscarinic antagonist (LAMA) monotherapy, a type of bronchodilator also known as a long-acting anticholinergic.

Incruse Ellipta is specifically indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.

Incruse Ellipta is supplied as a powder for inhalation via a plastic inhaler. The recommended dose is 1 inhalation once daily by the orally inhaled route only. It should be taken at the same time every day. Do not use Incruse Ellipta more than 1 time every 24 hours.

Mechanism of Action

Incruse Ellipta (umeclidinium) 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 the inhibition of M3 receptor 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. In preclinical in vitro as well as in vivo studies, prevention of methacholine and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of umeclidinium is predominantly a site-specific effect.

Side Effects

Adverse effects associated with the use of Incruse Ellipta may include, but are not limited to, the following:

• nasopharyngitis
• upper respiratory tract infection
• cough
• arthralgia

Trial Results

The FDA approval of Incruse Ellipta was based on dose-ranging trials in 624 subjects with COPD and two placebo-controlled confirmatory trials in 1,738 subjects with COPD.
Dose-ranging trials
Dose selection for umeclidinium in COPD was supported by a 7-day, randomized, double-blind, placebo-controlled, crossover trial evaluating 4 doses of umeclidinium (15.6 to 125 mcg) or placebo dosed once daily in the morning in subjects with COPD. A dose ordering was observed, with the 62.5- and 125-mcg doses demonstrating larger improvements in FEV1 over 24 hours compared with the lower doses of 15.6 and 31.25 mcg. The differences in trough FEV1 from baseline after 7 days for placebo and the 15.6-, 31.25-, 62.5-, and 125-mcg doses were -74 mL, 38 mL, 27 mL, 49 mL and 109 mL respectively. Two additional dose-ranging trials in subjects with COPD demonstrated minimal additional benefit at doses above 125 mcg. The dose-ranging results supported the evaluation of 2 doses of umeclidinium, 62.5 and 125 mcg, in the confirmatory COPD trials to further assess dose response.
Confirmatory Trials
Two randomized, double-blind, placebo-controlled, parallel-group trials were conducted to evaluate the efficacy of Incruse Ellipta on lung function. Trial I was a 24-week placebo controlled trial and Trial 2 was a 12-week placebo controlled trial. Trial 1 evaluated umeclidinium 62.5 mcg and placebo. The primary endpoint was change from baseline in trough (predose) FEV1 at Day 169 (defined as the mean of the FEV1 values obtained at 23 and 24 hours after the previous dose on Day 168) compared with placebo. Incruse Ellipta 62.5 mcg demonstrated a larger increase in mean change from baseline in trough (predose) FEV1 relative to placebo. In Trial 1, the mean peak FEV1 (over the first 6 hours relative to baseline) at Day 1 and at Day 168 for the group receiving umeclidinium 62.5 mcg compared with placebo was 126 and 130 mL, respectively. Similar results were obtained in Trial 2.