Safety and tolerability of srx246, a vasopressin 1a antagonist, in irritable huntington’s disease patients—a randomized phase 2 clinical trial

SRX246 is a vasopressin (AVP) 1a receptor antagonist that crosses the blood‐brain barrier. It reduced impulsive aggression, fear, depression and anxiety in animal models, blocked the actions of intranasal AVP on aggression/fear circuits in an experimental medicine fMRI study and demonstrated excellent safety in Phase 1 multiple‐ascending dose clinical trials. The present study was a 3‐arm, multicenter, randomized, placebo‐controlled, double‐blind, 12‐week, dose escalation study of SRX246 in early symptomatic Huntington’s disease (HD) patients with irritability. Our goal was to determine whether SRX246 was safe and well tolerated in these HD patients given its potential use for the treatment of problematic neuropsychiatric symptoms. Participants were randomized to receive placebo or to escalate to 120 mg twice daily or 160 mg twice daily doses of SRX246. Assessments included standard safety tests, the Unified Huntington’s Disease Rating Scale (UHDRS), and exploratory measures of problem behaviors. The groups had comparable demographics, features of HD and baseline irritability. Eighty‐two out of 106 subjects randomized completed the trial on their assigned dose of drug. One‐sided exact‐method confidence interval tests were used to reject the null hypothesis of inferior tolerability or safety for each dose group vs. placebo. Apathy and suicidality were not affected by SRX246. Most adverse events in the active arms were considered unlikely to be related to SRX246. The compound was safe and well tolerated in HD patients and can be moved forward as a candidate to treat irritability and aggression. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Magnetic resonance imaging (MRI): a technique to study flow an microstructure of concentrated emulsions

Nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) have recently been recognized as important techniques for R&D of products and processes, as is attested by several successful applications in different areas of chemical engineering in recent years. In this article we present new experimental methods based on MRI to study flow and microstructure of concentrated emulsions. The objective is to present the unique features of this noninvasive technique to accurately measure different properties of flowing particulate opaque systems. Experimental results of velocity profiles, spatial distribution of droplet sizes and spatial homogeneity of an oil-in-water dispersion in a horizontal, concentric cylinder geometry using different pulse sequences are presented. The application of these techniques allowed probing important information on flow and microstructure of multiphase systems of interest in chemical engineering and food science