Assessment Of Safety And Pharmacokinetic Profile Of A Novel Fixed Combination Of Glycopyrrolate And Formoterol HFA MDI In Healthy Volunteers

Abstract

Rationale: This first-in-human study provided safety and pharmacokinetic (PK) data on a novel fixed dose combination of Glycopyrrolate and Formoterol Fumarate metered dose inhaler (MDI). Pearl’s novel porous particle based suspension technology allows better targeting of drugs to the airways via pressurized metered dose inhaler (MDI), and enables the development of combination products with improved physical stability, content uniformity, and aerodynamic size distribution similarity across the combination drug components. The objective of this study was to provide safety and PK evidence in support of further clinical studies in patients with COPD. Methods: Study PT0030901 was a randomized, double-blind, single-dose, 4-period crossover, single-center study in healthy subjects that evaluated a single administration of 4 inhaled treatments: glycopyrrolate 72 μg (GP), formoterol fumarate 9.6 μg (FF), the fixed combination GP/FF from a single MDI, and the loose combination of GP + FF administered from two separate MDIs. At each treatment visit, subjects were assessed for 12 hours after dosing. There was a minimum 7 day washout period between treatments. Evaluations included adverse events (AEs), dry mouth and tremor assessments, hematology, clinical chemistry, vital signs, 12-lead electrocardiograms (ECG), spirometry, physical examinations, and PK parameters. Results: Sixteen subjects (11 females, 5 males), average age 27 years (range 19 to 47), were enrolled with 13 subjects completing all treatment periods. No important safety trends or signals were noted for GP/FF MDI fixed dose combination in terms of AEs, changes in serum potassium or other laboratory values, vital signs, ECGs, or spirometry parameters. Conclusions: The novel GP/FF MDI fixed dose combination was safe and well-tolerated, with a safety profile similar to that observed with the components administered individually or at the same time as a loose combination. These safety findings support further evaluation of GP/FF MDI in patients with COPD.