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Randomised clinical study: GR-MD-02, a galectin-3 inhibitor, vs. placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis.
- Source :
-
Alimentary pharmacology & therapeutics [Aliment Pharmacol Ther] 2016 Dec; Vol. 44 (11-12), pp. 1183-1198. Date of Electronic Publication: 2016 Oct 24. - Publication Year :
- 2016
-
Abstract
- Background: Non-alcoholic steatohepatitis (NASH) and resultant liver fibrosis is a major health problem without approved pharmacotherapy. Pre-clinical results of GR-MD-02, a galectin-3 inhibitor, suggested potential efficacy in NASH with advanced fibrosis/cirrhosis and prompted initiation of a clinical development programme in NASH with advanced fibrosis.<br />Aim: To evaluate the safety, pharmacokinetics and exploratory pharmacodynamic markers of GR-MD-02 in subjects having NASH with bridging fibrosis.<br />Methods: The GT-020 study was a first-in-human, sequential dose-ranging, placebo controlled, double-blinded study with the primary objective to assess the safety, tolerability and dose limiting toxicity of GR-MD-02, in subjects with biopsy-proven NASH with advanced fibrosis (Brunt stage 3). The secondary objectives were to characterise first-dose and multiple-dose pharmacokinetic profiles and to evaluate changes in potential serum biomarkers and liver stiffness as assessed by FibroScan.<br />Results: GR-MD-02 single and three weekly repeated of 2, 4 and 8 mg/kg revealed no meaningful clinical differences in treatment emergent adverse events, vital signs, electrocardiographic findings or laboratory tests. Pharmokinetic parameters showed a dose-dependent relationship with evidence of drug accumulation following 8 mg/kg (~twofold).<br />Conclusions: GR-MD-02 doses were in the upper range of the targeted therapeutic dose determined from pre-clinical data and were safe and well tolerated with evidence of a pharmacodynamic effect. These results provide support for a Phase 2 development programme in advanced fibrosis due to NASH.<br /> (© 2016 John Wiley & Sons Ltd.)
- Subjects :
- Adult
Aged
Biomarkers blood
Double-Blind Method
Female
Galectin 3 blood
Humans
Liver Cirrhosis blood
Male
Middle Aged
Non-alcoholic Fatty Liver Disease blood
Galectin 3 antagonists & inhibitors
Liver Cirrhosis drug therapy
Non-alcoholic Fatty Liver Disease drug therapy
Pectins adverse effects
Pectins blood
Pectins pharmacokinetics
Pectins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2036
- Volume :
- 44
- Issue :
- 11-12
- Database :
- MEDLINE
- Journal :
- Alimentary pharmacology & therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 27778367
- Full Text :
- https://doi.org/10.1111/apt.13816