Abstract
Intraoperative ureter identification helps reduce the risk of ureteral injury. Currently, no suitable agents for real-time ureter visualization are approved. ASP5354 (TK-1) is a novel indocyanine green derivative. In this first-in-human phase 1, double-blind, sequential ascending-dose study, urethral catheters were placed in 6 healthy volunteers who were randomized to single-dose, intravenous ASP5354 0.1 mg (n = 4) or placebo (n = 2). Sequential dose escalations to 0.5-, 2-, 8-, and 24-mg ASP5354 in new cohorts were contingent upon Dose-Escalation Committee approval after review of pharmacokinetic (PK) and safety data. Blood and urine samples were collected over 24 hours following dose administration. Objectives were to assess the safety/tolerability and PK of ASP5354. Treatment-emergent adverse events (TEAEs) were reported in 3 (15%) and 2 (20%) participants in the ASP5354 and placebo groups, respectively. In the former, there were 6 TEAEs (5/6 grade 1-2). One ASP5354 participant experienced grade 3 pyelonephritis, attributed to the catheter. No TEAEs were related to ASP5354. Mean plasma terminal elimination half-life ranged from 2.1 to 3.6 hours, with near complete urinary excretion of unchanged ASP5354 within 24 hours after administration. Linear and dose-proportional PK were observed. These results support further evaluation of ASP5354 at doses up to 24 mg for intraoperative near-infrared fluorescence ureter visualization.