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 & 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 & 400μg, v indacaterol (IND) 150μg & 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 & 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) & 56.2 pg/mL (400μg); T max: 0.5 hrs; AUC(0-t) 20.5pg*h/mL (100μg) & 127pg*h/mL (400μg). Conclusion Both AZD8999 doses were safe and well tolerated. A good efficacy profile was observed over 24 hours.