A randomized, double-blind, placebo controlled, single and multiple dosing, dose-escalation phase 1 clinical trial to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic characteristics and food effect after oral administration of HGR4113 in healthy subjects

开始日期2023-01-02

申办/合作机构

Glaceum

NCT05642377 / Recruiting临床1期

A Randomized, Double-Blind, Placebo Controlled, Single and Multiple Dosing, Dose-Escalation Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Characteristics and Food Effect After Oral Administration of HGR4113 in Healthy Subjects

Study Objective: The objective of this study is to evaluate the safety, tolerability, pharmacokinetic/pharmacodynamic characteristics, and food effect of HGR4113 after single and multiple oral administration in healthy subjects.
Study Design and Plan: This study is a randomized, double-blind, placebo controlled, single and multiple dosing, dose-escalation phase 1 clinical trial. Volunteers who have been deemed eligible based on the inclusion/exclusion criteria will be given a random number. Each subject will be assigned to one of the dose groups in a 6:2 ratio to HGR4113 (active) or placebo. Subjects will be studied in a double-blind manner and will receive the investigational product per protocol. Dose will be escalated once safety data is collected up to the last pharmacokinetic blood collection timepoint and safety and tolerability has been deemed acceptable following the review of the Safety Review Committee. Assessments including vital signs, 12-lead ECG, clinical laboratory, reproductive hormones, physical examination, and monitoring of adverse events concomitant medications will be conducted to evaluate safety and tolerability. Blood will be collected to evaluate the pharmacokinetic/pharmacodynamic characteristics.

开始日期2022-11-22

申办/合作机构

Glaceum

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100 项与 HGR-4113 相关的临床结果

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100 项与 HGR-4113 相关的转化医学

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100 项与 HGR-4113 相关的专利（医药）

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项与 HGR-4113 相关的文献（医药）

2023-06-08·Pharmaceutics

Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer.

Article

作者: Rehman, Shaheed Ur ; Yoo, Hye Hyun ; Seo, Jeong In ; Park, Hyung Soon ; Ha, Eun Ji ; Yoo, Sang-Ku

Drug solubility limits intravenous dosing for poorly water-soluble medicines, which misrepresents their bioavailability estimation. The current study explored a method using a stable isotope tracer to assess the bioavailability of drugs that are poorly water-soluble. HGR4113 and its deuterated analog, HGR4113-d7, were tested as model drugs. To determine the level of HGR4113 and HGR4113-d7 in rat plasma, a bioanalytical method using LC-MS/MS was developed. The HGR4113-d7 was intravenously administered to rats that were orally pre-administered HGR4113 at different doses; subsequently, the plasma samples were collected. HGR4113 and HGR4113-d7 were simultaneously determined in the plasma samples, and bioavailability was calculated using plasma drug concentration values. The bioavailability of HGR4113 was 53.3% ± 19.5%, 56.9% ± 14.0%, and 67.8% ± 16.7% after oral dosages of 40, 80, and 160 mg/kg, respectively. By eliminating the differences in clearance between intravenous and oral dosages at different levels, acquired data showed that the current method reduced measurement errors in bioavailability when compared to the conventional approach. The present study suggests a prominent method for evaluating the bioavailability of drugs with poor aqueous solubility in preclinical studies.

Molecules

Synthetic Glabridin Derivatives Inhibit LPS-Induced Inflammation via MAPKs and NF-κB Pathways in RAW264.7 Macrophages

Article

作者: Park, Hyung Soon ; Lee, Hyeong Min ; Choi, Leo Sungwong ; Ko, Wonmin ; Jeon, Hyun Ju ; Shin, Jaejin ; Kim, Kwan-Woo ; Kim, Sang Hyo ; Oh, Hyuncheol

Glabridin is a polyphenolic compound with reported anti-inflammatory and anti-oxidative effects. In the previous study, we synthesized glabridin derivatives—HSG4112, (S)-HSG4112, and HGR4113—based on the structure–activity relationship study of glabridin to improve its biological efficacy and chemical stability. In the present study, we investigated the anti-inflammatory effects of the glabridin derivatives in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We found that the synthetic glabridin derivatives significantly and dose-dependently suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2), and decreased the level of inducible nitric oxygen synthase (iNOS) and cyclooxygenase-2 (COX-2) and the expression of pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α). The synthetic glabridin derivatives inhibited the nuclear translocation of the NF-κB by inhibiting phosphorylation of the inhibitor of κB alpha (IκB-α), and distinctively inhibited the phosphorylation of ERK, JNK, and p38 MAPKs. In addition, the compounds increased the expression of antioxidant protein heme oxygenase (HO-1) by inducing nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) through ERK and p38 MAPKs. Taken together, these results indicate that the synthetic glabridin derivatives exert strong anti-inflammatory effects in LPS-stimulated macrophages through MAPKs and NF-κB pathways, and support their development as potential therapeutics against inflammatory diseases.

100 项与 HGR-4113 相关的药物交易

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