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Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.

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.

SUBMITTER: Brownstein MJ

PROVIDER: S-EPMC7696926 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.

Brownstein Michael J MJ Simon Neal G NG Long Jeffrey D JD Yankey Jon J Maibach Hilda T HT Cudkowicz Merit M Coffey Christopher C Conwit Robin A RA Lungu Codrin C Anderson Karen E KE Hersch Steven M SM Ecklund Dixie J DJ Damiano Eve M EM Itzkowitz Debra E DE Lu Shifang S Chase Marianne K MK Shefner Jeremy M JM McGarry Andrew A Thornell Brenda B Gladden Catherine C Costigan Michele M O'Suilleabhain Padraig P Marshall Frederick J FJ Chesire Amy M AM Deritis Paul P Adams Jamie L JL Hedera Peter P Lowen Kelly K Rosas H Diana HD Hiller Amie L AL Quinn Joseph J Keith Kellie K Duker Andrew P AP Gruenwald Christina C Molloy Angela A Jacob Cara C Factor Stewart S Sperin Elaine E Bega Danny D Brown Zsazsa R ZR Seeberger Lauren C LC Sung Victor W VW Benge Melanie M Kostyk Sandra K SK Daley Allison M AM Perlman Susan S Suski Valerie V Conlon Patricia P Barrett Matthew J MJ Lowenhaupt Stephanie S Quigg Mark M Perlmutter Joel S JS Wright Brenton A BA Most Elaine E Schwartz Guy J GJ Lamb Jessica J Chuang Rosalind S RS Singer Carlos C Marder Karen K Moran Joyce A JA Singleton John R JR Zorn Meghan M Wall Paola V PV Dubinsky Richard M RM Gray Carolyn C Drazinic Carolyn C

Journal of clinical medicine 20201116 11

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 earl ...[more]

PMID: 33207828

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Dataset Information

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.

Publications

Safety and Tolerability of SRX246, a Vasopressin 1a Antagonist, in Irritable Huntington's Disease Patients-A Randomized Phase 2 Clinical Trial.

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