{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T17:11:17Z","timestamp":1780593077031,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T00:00:00Z","timestamp":1663804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Diseases and Stroke SBIR Fast-track","doi-asserted-by":"publisher","award":["U44NS090616"],"award-info":[{"award-number":["U44NS090616"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Diseases and Stroke SBIR Fast-track","doi-asserted-by":"publisher","award":["U01NS077179"],"award-info":[{"award-number":["U01NS077179"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Diseases and Stroke SBIR Fast-track","doi-asserted-by":"publisher","award":["U01NS077352"],"award-info":[{"award-number":["U01NS077352"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CHDI Foundation","award":["U44NS090616"],"award-info":[{"award-number":["U44NS090616"]}]},{"name":"CHDI Foundation","award":["U01NS077179"],"award-info":[{"award-number":["U01NS077179"]}]},{"name":"CHDI Foundation","award":["U01NS077352"],"award-info":[{"award-number":["U01NS077352"]}]},{"name":"Azevan Pharmaceuticals, Inc.","award":["U44NS090616"],"award-info":[{"award-number":["U44NS090616"]}]},{"name":"Azevan Pharmaceuticals, Inc.","award":["U01NS077179"],"award-info":[{"award-number":["U01NS077179"]}]},{"name":"Azevan Pharmaceuticals, Inc.","award":["U01NS077352"],"award-info":[{"award-number":["U01NS077352"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>SRX246, an orally available CNS penetrant vasopressin (VP) V1a receptor antagonist, was studied in Huntington\u2019s disease (HD) patients with irritability and aggressive behavior in the exploratory phase 2 trial, Safety, Tolerability, and Activity of SRX246 in Irritable HD patients (STAIR). This was a dose-escalation study; subjects received final doses of 120 mg BID, 160 mg BID, or placebo. The compound was safe and well tolerated. In this paper, we summarize the results of exploratory analyses of measures of problematic behaviors, including the Cohen\u2013Mansfield Agitation Inventory (CMAI), Aberrant Behavior Checklist (ABC), Problem Behaviors Assessment-short form (PBA-s), Irritability Scale (IS), Clinical Global Impression (CGI), HD Quality of Life (QoL), and Caregiver Burden questionnaires. In addition to these, we asked subjects and caregivers to record answers to short questions about mood, irritability, and aggressive conduct in an eDiary. STAIR was the first rigorously designed study of behavioral endpoints like these in HD. The exploratory analyses showed that SRX246 reduced aggressive acts. Readily observed behaviors should be used as trial endpoints.<\/jats:p>","DOI":"10.3390\/jpm12101561","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T21:10:05Z","timestamp":1663881005000},"page":"1561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Vasopressin 1a Receptor Antagonist SRX246 Reduces Aggressive Behavior in Huntington\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Hilda T.","family":"Maibach","sequence":"first","affiliation":[{"name":"Azevan Pharmaceuticals Inc., Bethlehem, PA 18015, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Brownstein","sequence":"additional","affiliation":[{"name":"Azevan Pharmaceuticals Inc., Bethlehem, PA 18015, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5948-6672","authenticated-orcid":false,"given":"Steven M.","family":"Hersch","sequence":"additional","affiliation":[{"name":"Eisai Pharmaceuticals, Nutley, NJ 07110, USA"},{"name":"Formerly at Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen E.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Department of Neurology, Medstar Georgetown University Hospital, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra E.","family":"Itzkowitz","sequence":"additional","affiliation":[{"name":"Azevan Pharmaceuticals Inc., Bethlehem, PA 18015, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve M.","family":"Damiano","sequence":"additional","affiliation":[{"name":"Azevan Pharmaceuticals Inc., Bethlehem, PA 18015, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal G.","family":"Simon","sequence":"additional","affiliation":[{"name":"Azevan Pharmaceuticals Inc., Bethlehem, PA 18015, USA"},{"name":"Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"N\u00f3brega, C., and Pereira de Almeida, L. 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