Pharmacokinetics and safety of a single dose of the novel necrosis inhibitor LC28‐0126 in healthy male subjects

Aims

A novel necrosis inhibitor, LC28‐0126, is expected to have a cellular protective effect from ischaemic reperfusion injury in acute myocardial infarction. The objective of this study was to investigate the safety, tolerability and pharmacokinetics of LC28‐0126 after a single intravenous administration in healthy male subjects.

Methods

The study was a dose‐block‐randomized, double‐blind, placebo‐controlled, single ascending dose, first‐in‐human trial. Subjects were randomly assigned to receive 0.3, 1, 3, 10, 25, 50, 100 or 200 mg of LC28‐0126. LC28‐0126 was infused for 30 min and 5 min in cohorts 1 and 2, respectively. An interim analysis to assess the tolerability and pharmacokinetics was conducted in each dose group. Blood samples were taken to determine plasma LC28‐0126 concentrations from predose to 48 or 144 h postdose, and urine samples were taken from predose to 48 or 72 h postdose.

Results

Overall, 89 subjects were randomly assigned to the dose groups of the two cohorts. LC28‐0126 was well tolerated, and no serious adverse events were reported. LC28‐0126 showed rapid disposition in the distribution phase. Overall, the fraction of unchanged LC28‐0126 excreted during the 48 or 72 h after administration was below 5%. The systemic exposure of LC28‐0126 tends to be increased in a dose‐proportional manner in the dose range of 0.3–200 mg.

Conclusions

A single intravenous dose of LC28‐0126 was safe and well tolerated up to 200 mg. Furthermore, LC28‐0126 demonstrated a predictable pharmacokinetic profile after a single intravenous infusion of doses ranging from 0.3 to 200 mg.

DOI: 10.1111/bcp.13213

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