@article{ref1,
title="Safety and tolerability of srx246, a vasopressin 1a antagonist, in irritable huntington's disease patients--a randomized phase 2 clinical trial",
journal="Journal of clinical medicine",
year="2020",
author="Brownstein, M.J. and Simon, N.G. and Long, J.D. and Yankey, J. and Maibach, H.T. and Cudkowicz, M. and Coffey, C. and Conwit, R.A. and Lungu, C. and Anderson, K.E. and Hersch, S.M. and Ecklund, D.J. and Damiano, E.M. and Itzkowitz, D.E. and Lu, S. and Chase, M.K. and Shefner, J.M. and McGarry, A. and Thornell, B. and Gladden, C. and Costigan, M. and O'suilleabhain, P. and Marshall, F.J. and Chesire, A.M. and Deritis, P. and Adams, J.L. and Hedera, P. and Lowen, K. and Diana Rosas, H. and Hiller, A.L. and Quinn, J. and Keith, K. and Duker, A.P. and Gruenwald, C. and Molloy, A. and Jacob, C. and Factor, S. and Sperin, E. and Bega, D. and Brown, Z.R. and Seeberger, L.C. and Sung, V.W. and Benge, M. and Kostyk, S.K. and Daley, A.M. and Perlman, S. and Suski, V. and Conlon, P. and Barrett, M.J. and Lowenhaupt, S. and Quigg, M. and Perlmutter, J.S. and Wright, B.A. and Most, E. and Schwartz, G.J. and Lamb, J. and Chuang, R.S. and Singer, C. and Marder, K. and Moran, J.A. and Singleton, J.R. and Zorn, M. and Wall, P.V. and Dubinsky, R.M. and Gray, C. and Drazinic, C.",
volume="9",
number="11",
pages="1-14",
abstract="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.<p /><p>Language: en</p>",
language="en",
issn="2077-0383",
doi="10.3390/jcm9113682",
url="http://dx.doi.org/10.3390/jcm9113682"
}