Bronchodilator effects, pharmacokinetics and safety of PSX1002-GB, a novel glycopyrronium bromide formulation, in COPD patients; a randomised crossover study

AimsTo establish the dose–response relationship for pharmacodynamics (bronchodilatation), safety and pharmacokinetics of a novel particle engineered formulation of Glycopyrronium bromide (PSX1002-GB) in patients with chronic obstructive pulmonary disease (COPD).MethodsPatients with moderate to severe COPD with bronchodilator reversible lung function were enrolled into this randomized, placebo-controlled, double-blind, dose-ranging, single dose, five way cross-over study (n = 37). Patients received single doses of PSX1002-GB (12.5–100 μg) via pMDI with one-week washouts between treatments.ResultsPSX1002-GB caused a bronchodilator response observed at 5 min post-dose at all doses. Significant improvements in mean change from baseline FEV1 at 24 h were seen at all doses compared with placebo; Mean changes were 0.071L (95% CI 0.041–0.101), 0.087L (95% CI 0.056–0.118), 0.102L (95% CI 0.072–0.133) and 0.120L (95% CI 0.089–0.150) for 12.5, 25, 50 and 100 μg respectively. PSX1002-GB 50 and 100 mcg caused rapid bronchodilation at 5 min after dosing. PSX1002-GB was well tolerated with similar adverse event rates reported compared to placebo. There were no clinically relevant changes in heart rate, blood pressure or ECG parameters (including QTc interval).ConclusionSingle doses of PSX1002-GB (12.5–100 μg) were well tolerated. PSX1002-GB 50 and 100 mcg delivered by pMDI produced rapid onset bronchodilation that was sustained over a 24 h period.