The pharmacodynamics of GSK961081 in patients with COPD

Introduction: GSK961081 is a dual pharmacophore with both muscarinic antagonist and beta 2 agonist (MABA) activity. Objective: To assess the pharmacodynamics of GSK961081. Methods: This was a randomised, double-blind, double-dummy, placebo-controlled, incomplete block crossover study in 50 COPD patients. Patients were randomised to 3 of 4 possible treatments: 400μg GSK961081 once daily (OD) (n=29); 1200μg GSK961081 OD (n=32); salmeterol 50μg twice daily+tiotropium 18μg OD (SAL+TIO) (n=41); and placebo (n=43) by inhalation for 14 days. Pharmacodynamics (lung and systemic), safety and tolerability were monitored. Results: After 14 days9 dosing there were significant improvements in trough FEV 1 for all active treatments. For 400μg GSK961081, 1200μg GSK961081 and SAL+TIO mean (95% CI) differences vs placebo were 0.115L (0.024,0.205), 0.168L (0.080,0.255) and 0.103L (0.026,0.180), respectively (all p Conclusions: GSK961081 was well tolerated and showed significant bronchodilatation, meriting further evaluation as a potential therapy for COPD. Funded by GSK (MAB104958; NCT00478738)