PI-004 - SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF A NOVEL MACROCYCLIC GADOLINIUM-BASED CONTRAST AGENT, HNP-2006, AFTER A SINGLE INTRAVENOUS ADMINISTRATION IN HEALTHY SUBJECTS.

J. Oh¹, K. Huh², S. Hwang¹, J. Oh³, Y. Lee⁴, H. Lee⁴, K. Yu², S. Lee²; ¹Seoul National University Hospital, Seoul, Republic of Korea, ²Seoul National University Bundang Hospital, Seoul, Republic of Korea, ³Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea, ⁴Hana Pharm Co., Ltd., Seoul, Republic of Korea.

Background: HNP-2006, a novel macrocyclic gadolinium-based contrast agent, showed high relaxivity, stability and superior tissue contrast profile without free gadolinium release in preclinical studies. This study aimed to evaluate the safety, tolerability, and pharmacokinetics (PKs) of HNP-2006 after a single intravenous (IV) administration in healthy subjects.

Methods: A randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects randomly received a single IV administration of HNP-2006 or placebo at a ratio of 6:2 in 5 dose groups (0.02, 0.05, 0.10, 0.20, 0.30 mmol/kg). Blood and urine samples for PK assessment were collected up to 72 hours. Plasma and urine HNP-2006 concentrations were determined using validated liquid chromatography-tandem mass spectrometry. PK parameters were calculated using noncompartmental methods. Routine safety and tolerability assessments were performed throughout the study.

Results: A total of 40 subjects completed the study. HNP-2006 was mostly excreted in urine as unchanged form (~100%). The elimination half-life was relatively short and no significant difference between the dose groups. Volume of distribution was consistent across the entire dose group. The systemic exposure of HNP-2006 was increased in a dose-proportional manner. In terms of safety, treatment emergent adverse events (TEAEs) were all mild in severity and the incidence of TEAEs was associated with the dose strength. Nausea and dizziness were the most common TEAEs, occurring immediately after administration. No significant renal function decrease was observed.

Conclusion: A single IV administration of HNP-2006 was safe and well-tolerated up to 0.30 mmol/kg. HNP-2006 was linear in PK, and predominantly excreted in urine with a short half-life.