1. Inhibition of 11β‐Hydroxysteroid dehydrogenase‐1 with <scp>AZD4017</scp> in patients with nonalcoholic steatohepatitis or nonalcoholic fatty liver disease: A randomized, double‐blind, placebo‐controlled, phase <scp>II</scp> study
- Author
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Yogesh Yadav, Kelly Dunagan, Rachita Khot, Sudhakar K. Venkatesh, John Port, Alfonso Galderisi, Claudio Cobelli, Craig Wegner, Ananda Basu, Rickey Carter, and Rita Basu
- Subjects
Niacinamide ,Endocrinology ,Diabetes Mellitus, Type 2 ,Double-Blind Method ,Liver ,Piperidines ,Non-alcoholic Fatty Liver Disease ,Endocrinology, Diabetes and Metabolism ,11-beta-Hydroxysteroid Dehydrogenase Type 1 ,Internal Medicine ,Humans - Abstract
To evaluate whether short-term treatment with a selective 11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) inhibitor, AZD4017, would block hepatic cortisol production and thereby decrease hepatic fat in patients with nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), with or without type 2 diabetes (T2D).This was a randomized, double-blind, placebo-controlled, phase 2 study conducted at two sites. Key inclusion criteria were the presence of NAFLD or NASH on magnetic resonance imaging (MRI) or recent biopsy positive for NASH. Enrolled patients were randomly assigned (1:1) to AZD4017 or placebo for 12 weeks. Primary outcomes were between-group differences in mean change from baseline to week 12 in liver fat fraction (LFF) and conversion ofA total of 93 patients were randomized; 85 patients completed treatment. The mean (standard deviation [SD]) change in LFF was -0.667 (5.246) and 0.139 (4.323) in the AZD4017 and placebo groups (P = 0.441). For patients with NASH and T2D, the mean (SD) change in LFF was significantly improved in the AZD4017 versus the placebo group (-1.087 [5.374] vs. 1.675 [3.318]; P = 0.033). Conversion ofAlthough the study did not meet one of the primary outcomes, AZD4017 blocked the conversion of
- Published
- 2022
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