Seokuee Kim1, Hyewon Chung1, SeungHwan Lee1, Sang-Heon Cho2, Hyun-Jai Cho3, Soon Ha Kim4, In-Jin Jang1, Kyung-Sang Yu1. 1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea. 2. Department of Clinical Pharmacology, Inha University School of Medicine and Hospital, Incheon, South Korea. 3. Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine and Hospital, Seoul, South Korea. 4. R&D Park, LG Life Sciences Ltd, Daejeon, South Korea.
Abstract
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.
RCT Entities:
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.
Authors: Hyoung Jin Kim; Sun Young Koo; Bong-Hyun Ahn; Oeuk Park; Doo Hoe Park; Dong Ook Seo; Jong Heon Won; Hyeon Joo Yim; Hyo-Shin Kwak; Heui Sul Park; Chul Woong Chung; Young Leem Oh; Soon Ha Kim Journal: Arch Pharm Res Date: 2010-11-30 Impact factor: 4.946
Authors: Frans Van de Werf; Jeroen Bax; Amadeo Betriu; Carina Blomstrom-Lundqvist; Filippo Crea; Volkmar Falk; Gerasimos Filippatos; Keith Fox; Kurt Huber; Adnan Kastrati; Annika Rosengren; P Gabriel Steg; Marco Tubaro; Freek Verheugt; Franz Weidinger; Michael Weis Journal: Eur Heart J Date: 2008-11-12 Impact factor: 29.983