title: Bronchodilator effects, pharmacokinetics and safety of PSX1002-GB, a novel glycopyrronium bromide formulation, in COPD patients; a randomised crossover study.
abstract: To 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).
  
  
  
  Patients 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.
  
  
  
  PSX1002-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).
  
  
  
  Single 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.
authors.affiliation: University of Manchester, Medicines Evaluation Unit Limited, The Langley Building, Wythenshawe Hospital, Southmoor Road, M23 9QZ, UK.
authors.forename: Dave
authors.initials: D
authors.lastname: Singh
authors.affiliation: University of Manchester, Medicines Evaluation Unit Limited, The Langley Building, Wythenshawe Hospital, Southmoor Road, M23 9QZ, UK. Electronic address: ARavi@meu.org.uk.
authors.forename: Arjun
authors.initials: A
authors.lastname: Ravi
authors.affiliation: University of Manchester, Medicines Evaluation Unit Limited, The Langley Building, Wythenshawe Hospital, Southmoor Road, M23 9QZ, UK.
authors.forename: Frederick
authors.initials: F
authors.lastname: Reid
authors.affiliation: ClinPsy Limited, St. Albans, Hertfordshire, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: Buck
authors.affiliation: The Clinical Trial Company, Knutsford, Cheshire, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: O'Connor
authors.affiliation: Prosonix Limited (part of Circassia Limited, Oxford, UK), Oxford, UK.
authors.forename: Geoff
authors.initials: G
authors.lastname: Down
mesh_terms: D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006024:Glycopyrrolate / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D036501:Metered Dose Inhalers; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001993:Bronchodilator Agents; D006024:Glycopyrrolate
keywords: COPD; Glycopyrronium bromide; Long acting anti-muscarinic agent (LAMA); Pressurised metered-dose inhaler (pMDI)