Efficacy and safety of nebulised glycopyrrolate for administration using high efficiency nebuliser in patients with COPD.

AIMS: To establish the dose-response for pharmacodynamics (bronchodilatation), safety and pharmacokinetics for a nebulised formulation of the long-acting muscarinic antagonist glycopyrrolate (EP-101) with a high efficiency nebuliser in patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with moderate to severe COPD (GOLD II/III), with reversible lung function were enrolled into this randomised, double-blind, placebo-controlled, 6-period cross-over study (n=42). Patients received single doses of EP-101 (12.5-400μg) and placebo via a high efficiency nebuliser (eFlow(®) PARI nebuliser), with washout between treatments. Plasma pharmacokinetics were assessed in a subset of patients (n=11). RESULTS: All treatments were well tolerated with similar adverse event rates reported with placebo and at all doses. There were no clinically relevant changes in heart rate, systolic and diastolic blood pressure or in ECG parameters including QTc interval. Following treatment with EP-101 at all doses there was a rapid bronchodilator response within 5 minutes. Significant improvements in mean change from baseline FEV1 at 24 hours were reported at doses >50μg compared with placebo, with a clear dose response relationship. Mean change in FEV1 were 0.10L (0.06-0.14 95%CI) and 0.12L (0.08-0.16) for 100μg and 200μg respectively. CONCLUSION: Single doses of EP-101 ranging from 12.5μg to 400μg were well tolerated. EP-101 delivered by high efficiency nebuliser device produced a rapid onset of bronchodilatation with clinically meaningful improvements in lung function maintained over a 24 hour period at all doses >50μg.