AZD4604 PK assessment using finger-prick microsampling

The need for repeated phlebotomy in clinical trials is a significant burden for both participants and sites. Finger-prick blood (FPB) microsampling is a minimally invasive technique widely used for home-based blood sampling in routine clinical practice and may simplify assessment whilst facilitating decentralised trial designs. Concerns remain regarding the stability and reproducibility of FPB microsampling, particularly for PK assessment. AZD4604 is an inhaled Janus Kinase-1-selective inhibitor developed for the treatment of moderate-to-severe asthma, administered using a dry-powder inhaler. Safety, tolerability, and PK of AZD4604 after multiple administrations in healthy volunteers were evaluated in Phase 1 settings. FPB samples were collected alongside conventional venepuncture to investigate the feasibility and performance of such technique for PK analysis. FPB samples (250-500 µL) were collected using BD Microtainers EDTA tubes at 2 occasions. AZD4604 plasma concentrations from FPB and venous samples were determined using a validated bioanalytical method (LC-MS/MS). FPB samples were available from 10 healthy volunteers receiving multiple doses of AZD4604. FPB drug concentrations were within ±20% of those from venous blood for 13 out of 20 samples (65%). The overall ratio of drug concentrations ranged from 0.53 to 1.43. A linear relationship between both methods was observed (slope 0.75, adjusted R2 0.93, p-value <0.001). These results showed FPB-based PK assessment correlated well with conventional venepuncture. This data suggests that FPB sampling may be adequate to evaluate the PK of an inhaled drug. FPB sampling warrants further rigorous evaluation as an option to enable simplified and innovative clinical trial design, reducing burden on both sites and participants.