Golexanolone improves cognitive performance in hepatic encephalopathy
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Golexanolone was well tolerated and correlated with improvement in cognitive performance in patients with hepatic encephalopathy, according to a study published in the Journal of Hepatology.
“The findings therefore support a role for neurosteroids in the pathogenesis of [hepatic encephalopathy (HE)]-related sleepiness and vigilance in particular and indicate that golexanolone deserves further study as a potential treatment for neurosteroid-mediated vigilance and cognitive disorders including HE, either alone or in association with ammonia-lowering strategies,” Sara Montagnese, MD, PhD, professor of medicine from the University of Padova in Italy, and colleagues wrote.
Montagnese and colleagues identified patients with Child-Pugh A/B cirrhosis and abnormal continuous reaction time (CRT). They randomly assigned 12 patients to placebo and 33 patients to 3 weeks dosing with golexanolone (10, 40 or 80 mg twice daily).
“Golexanolone is a novel small molecule GABA-A receptor modulating steroid antagonist under development for treatment of cognitive and vigilance disorders due to allosteric over-activation of GABA-A receptors by neurosteroids,” the investigators wrote.
At baseline, 10 and 21 days, researchers obtained CRT, psychometric hepatic encephalopathy score (PHES), animal naming test (ANT), Epworth sleepiness scale (ESS) and electroencephalography (mean dominant frequency [MDF]; delta+theta/alpha+beta ratio [DT/AB]).
According to study results, golexanolone demonstrated satisfactory safety and pharmacokinetics. Investigators saw similar baseline characteristics between patients given placebo or golexanolone.
“By prespecified analyses, golexanolone was associated with directionally favorable changes vs. placebo in ESS (P = .047), MDF (P = .142) and DT/AB (P = .021),” Montagnese and colleagues wrote.
According to researchers, all patients demonstrated directionally favorable changes in CRT, PHES and ANT; however, there was no statistical difference between golexanolone and placebo.
Post hoc analyses showed an efficacy signal by cognitive measures after taking into consideration the variability and improvement in CRT, PHES and ANT observed between screening and baseline.
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