title: Pharmacokinetics and safety of a single dose of the novel necrosis inhibitor LC28-0126 in healthy male subjects.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
authors.forename: Seokuee
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Chung
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
authors.forename: SeungHwan
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology, Inha University School of Medicine and Hospital, Incheon, South Korea.
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
authors.forename: Hyun-Jai
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: R&D Park, LG Life Sciences Ltd, Daejeon, South Korea.
authors.forename: Soon Ha
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009336:Necrosis / Q000517:prevention & control*; D019055:No-Observed-Adverse-Effect Level; D055815:Young Adult
keywords: Phase I; clinical trials; drug safety; pharmacokinetics