A phase I multiple ascending dose study to assess the safety, tolerability and pharmacokinetics of AZD0530, a highly selective, orally available, dual-specific Src-Abl kinase inhibitor

3972 AZD0530 is a highly selective, dual-specific, orally available small molecule inhibitor of Src family kinases and Bcr-Abl. To assess the safety, tolerability and pharmacokinetic (PK) profile a multiple ascending dose study was conducted in healthy male volunteers. Sixty volunteers were randomised in cohorts of 12 to receive AZD0530 (n=9) or placebo (n=3) as a single dose (for PK) followed by a washout period and then multiple daily dosing for up to fourteen days. Doses up to 250mg/day were administered in this manner. Adverse events have been generally mild and have included rash, flu-like symptoms, myalgia, arthalgia, headache, loose stools and raised creatinine. A summary of the PK findings is as follows: Plasma concentrations remained above the predicted IC50 for Src kinases as predicted from pre-clinical modelling. In conclusion, AZD0530 is a small molecule inhibitor of Src family kinases and Bcr-Abl. The drug is tolerated when administered in multiple daily doses up to 250mg. The PK of AZD0530 is consistent with once daily oral dosing.