Abstract
Background: AZD5069 is a small molecule CXC chemokine receptor 2 (CXCR2) antagonist in development as a novel oral treatment for chronic obstructive pulmonary disease. The safety and tolerability of single ascending doses (SAD) of AZD5069 have been investigated in a first time in human Phase I, randomised, double-blind, parallel group, placebo-controlled study in healthy male and female adult volunteers (NCT00953888).
Methods: 69 volunteers were randomised in cohorts of up to 9 to receive either a single dose of AZD5069 (n=45) or placebo (n=24) after an overnight fast. Doses of AZD5069 were 0.1 mg, 0.5, 1.65, 5.45, 17.99, 60, 120 or 200 mg. Each volunteer was dosed only once.
Results: Reversible dose-related reductions in circulating neutrophil counts were observed by 8 hours post-dose, consistent with reported literature on CXCR2 inhibition. The reduction reached a plateau, beyond which increasing exposure had no further effect, but recovering by 96 hours post-dose, at all doses. The reductions were approximately dose related, but a direct relationship with drug concentration could not be confirmed from these data. The pharmacokinetics of AZD5069 were linear, approximately dose proportional and predictable up to 200 mg. Biomarker assay responses were +ve at 4 hrs post dose at > 5.45 mg, maximal at 120 mg.
AZD5069 was well tolerated. A total of 33 adverse events (AEs) was reported [23 AZD5069, 10 placebo], all of which were of mild-to-moderate intensity, except for one severe AE in the placebo group. Four AEs were considered drug-related: dry mouth (AZD5069 0.5 mg), nausea (AZD5069 120 mg), dysuria and headache (placebo).
Conclusion: AZD5069 was generally well tolerated in SAD in healthy volunteers.
- © 2011 ERS