Publications

@article{Newsome2020-vk,

title = {Volixibat in adults with non-alcoholic steatohepatitis: 24-week 

 interim analysis from a randomized, phase II study},

author = {Philip N Newsome and Melissa Palmer and Bradley Freilich and Muhammad Y Sheikh and Aasim Sheikh and Harry Sarles and Robert Herring and Parvez Mantry and Zeid Kayali and Tarek Hassanein and Hak-Myung Lee and Guruprasad P Aithal and Volixibat group},

year  = {2020},

date = {2020-08-01},

journal = {J. Hepatol.},

volume = {73},

number = {2},

pages = {231\textendash240},

publisher = {Elsevier BV},

abstract = {BACKGROUND \& AIMS: Volixibat is an inhibitor of the apical 

 sodium-dependent bile acid transporter (ASBT) that has been 

 hypothesized to improve non-alcoholic steatohepatitis (NASH) by 

 blocking bile acid reuptake and stimulating hepatic bile acid 

 production. We studied the safety, tolerability and efficacy of 

 volixibat in patients with NASH. METHODS: In this double-blind, 

 phase II dose-finding study, adults with $geq$5% steatosis and NASH without cirrhosis (N = 197) were randomized to receive 

 volixibat (5, 10 or 20 mg) or placebo once daily for 48 weeks. The endpoints of a predefined interim analysis (n = 80), at week 

 24, were: $geq$5% reduction in MRI-proton density fat fraction 

 and $geq$20% reduction in serum alanine aminotransferase 

 levels. The primary endpoint was a $geq$2-point reduction in 

 non-alcoholic fatty liver disease activity score without 

 worsening fibrosis at week 48. RESULTS: Volixibat did not meet 

 either interim endpoint; the study was terminated owing to lack 

 of efficacy. In participants receiving any volixibat dose, mean 

 serum 7-alpha-hydroxy-4-cholesten-3-one (C4; a biomarker of bile 

 acid synthesis) increased from baseline to week 24 (+38.5 ng/ml 

 [SD 53.18]), with concomitant decreases in serum total 

 cholesterol (-14.5 mg/dl [SD 28.32]) and low-density lipoprotein 

 cholesterol (-16.1 mg/dl [SD 25.31]). These changes were 

 generally dose-dependent. On histological analysis, a greater proportion of participants receiving placebo (38.5},

keywords = {Alanine aminotransferase, ASBT inhibitor, Humans, Non-alcoholic   fatty liver disease, Non-alcoholic steatohepatitis, Phase II, Steatosis},

pubstate = {published},

tppubtype = {article}

}