First in human randomised trial of J2H-1702 : A novel 11β-hydroxysteroid dehydrogenase type 1 inhibitor for non-alcoholic steatohepatitis treatment
© 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd..
BACKGROUND: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which is an enzyme that converts cortisone to cortisol, plays a role in the regulation of glucose metabolism and inflammation. J2H-1702 is a novel 11β-HSD1 inhibitor, and the inhibition of 11β-HSD1 has been shown to improve insulin sensitivity, reduce inflammation, and prevent the development of nonalcoholic steatohepatitis (NASH) in preclinical models.
AIMS: We aimed to assess the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of J2H-1702 after a single-dose oral administration.
METHODS: A randomised, double-blinded, placebo-controlled, single-dose, dose-escalation study was conducted on 50 healthy volunteers. Blood and urine samples were collected to assess the PK and PD of J2H-1702.
RESULTS: The peak plasma concentration of J2H-1702 was observed at 2-2.9 h after a single-dose oral administration. J2H-1702 reduced 11β-HSD1 activity compared to the placebo at all dose levels. The drug reached its maximal inhibitory effect within 12-24 h post-dose administration, and the inhibitory effect was maintained till 1 day after administration of the study drug. The drug showed typical first-order elimination kinetics, with a mean elimination half-life of 9.8-14.7 h. Systemic exposure to J2H-1702 increased in a dose-dependent manner. J2H-1702 was well tolerated after a single oral administration of up to 300 mg. A total of 11 treatment-emergent adverse events (TEAEs) occurred in seven (14%) participants, all of which were mild and resolved spontaneously. The most common TEAE was diarrhoea (8%), followed by dizziness (4%).
CONCLUSIONS: The results of this study suggest that J2H-1702 could be developed as an effective therapeutic option for NASH.
| Errataetall: |
CommentIn: Aliment Pharmacol Ther. 2023 Dec;58(11-12):1238-1239. - PMID 37986603 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:58 |
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| Enthalten in: |
Alimentary pharmacology & therapeutics - 58(2023), 11-12 vom: 20. Dez., Seite 1132-1142 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kim, Yun [VerfasserIn] |
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| Links: |
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| Themen: |
11-beta-Hydroxysteroid Dehydrogenase Type 1 |
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| Anmerkungen: |
Date Completed 22.11.2023 Date Revised 11.12.2023 published: Print-Electronic CommentIn: Aliment Pharmacol Ther. 2023 Dec;58(11-12):1238-1239. - PMID 37986603 Citation Status MEDLINE |
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| doi: |
10.1111/apt.17726 |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a First in human randomised trial of J2H-1702 |b A novel 11β-hydroxysteroid dehydrogenase type 1 inhibitor for non-alcoholic steatohepatitis treatment |
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| 500 | |a CommentIn: Aliment Pharmacol Ther. 2023 Dec;58(11-12):1238-1239. - PMID 37986603 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which is an enzyme that converts cortisone to cortisol, plays a role in the regulation of glucose metabolism and inflammation. J2H-1702 is a novel 11β-HSD1 inhibitor, and the inhibition of 11β-HSD1 has been shown to improve insulin sensitivity, reduce inflammation, and prevent the development of nonalcoholic steatohepatitis (NASH) in preclinical models | ||
| 520 | |a AIMS: We aimed to assess the pharmacokinetics (PKs), pharmacodynamics (PDs), safety, and tolerability of J2H-1702 after a single-dose oral administration | ||
| 520 | |a METHODS: A randomised, double-blinded, placebo-controlled, single-dose, dose-escalation study was conducted on 50 healthy volunteers. Blood and urine samples were collected to assess the PK and PD of J2H-1702 | ||
| 520 | |a RESULTS: The peak plasma concentration of J2H-1702 was observed at 2-2.9 h after a single-dose oral administration. J2H-1702 reduced 11β-HSD1 activity compared to the placebo at all dose levels. The drug reached its maximal inhibitory effect within 12-24 h post-dose administration, and the inhibitory effect was maintained till 1 day after administration of the study drug. The drug showed typical first-order elimination kinetics, with a mean elimination half-life of 9.8-14.7 h. Systemic exposure to J2H-1702 increased in a dose-dependent manner. J2H-1702 was well tolerated after a single oral administration of up to 300 mg. A total of 11 treatment-emergent adverse events (TEAEs) occurred in seven (14%) participants, all of which were mild and resolved spontaneously. The most common TEAE was diarrhoea (8%), followed by dizziness (4%) | ||
| 520 | |a CONCLUSIONS: The results of this study suggest that J2H-1702 could be developed as an effective therapeutic option for NASH | ||
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