LATE-BREAKING ABSTRACT: Single-dose safety, tolerability, PD & PK of AZD8999, a bi-functional muscarinic antagonist/β2-agonist (MABA), in patients with COPD

Background AZD8999 (formerly LAS190792) is a novel MABA bronchodilator in development for COPD treatment. Aims and objectives Phase I safety, tolerability, PD u0026 PK study of single doses of AZD8999, in patients with COPD. This investigation formed Part 2 of a First-in-Man study. Methods Randomised, double-blind, placebo-controlled, single-dose, 5-way complete crossover investigating safety/tolerability, PD of AZD8999 100μg u0026 400μg, v indacaterol (IND) 150μg u0026 tiotropium (TIO) 18μg in subjects with moderate to severe COPD (N=38). PK of AZD8999 was assessed in a subset of at least 10 evaluable patients. Results Both AZD8999 doses were safe and well tolerated. PD Statistically significant, clinically meaningful, sustained improvements in change from baseline in trough FEV 1 were seen for all treatments v placebo (178mL and 104mL with AZD8999 400μg and 100μg, respectively). Improvement was statistically significantly greater with AZD8999 400μg than AZD8999 100μg u0026 IND 150μg, and with TIO 18μg than AZD8999 100μg (Fig). PK AZD8999 plasma levels detected up to 2h (100μg) and 6h (400μg) post-dose. AZD8999 parameters: C max 15.4 pg/mL (100μg) u0026 56.2 pg/mL (400μg); T max: 0.5 hrs; AUC(0-t) 20.5pg*h/mL (100μg) u0026 127pg*h/mL (400μg). Conclusion Both AZD8999 doses were safe and well tolerated. A good efficacy profile was observed over 24 hours.