{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:39:56Z","timestamp":1789526396918,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Available essential tremor (ET) therapies have limitations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objective of this study was to evaluate CX\u20108998, a selective T\u2010type calcium channel modulator, in essential tremor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients 18\u201375\u2009years old with moderate to severe essential tremor were randomized 1:1 to receive CX\u20108998 (titrated to 10\u2009mg twice daily) or placebo. The primary end point was change from baseline to day 28 in The Essential Tremor Rating Assessment Scale performance subscale scored by independent blinded video raters. Secondary outcomes included in\u2010person blinded investigator rating of The Essential Tremor Rating Assessment Scale performance subscale, The Essential Tremor Rating Assessment Scale activities of daily living subscale, and Kinesia ONE accelerometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The video\u2010rated The Essential Tremor Rating Assessment Scale performance subscale was not different for CX\u20108998 (n\u00a0=\u00a039) versus placebo (n\u00a0=\u00a044; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.696). CX\u20108998 improved investigator\u2010rated The Essential Tremor Rating Assessment Scale performance subscale (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.017) and The Essential Tremor Rating Assessment Scale activities of daily living (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.049) but not Kinesia ONE (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.421). Adverse events with CX\u20108998 included dizziness (21%), headache (8%), euphoric mood (6%), and insomnia (6%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The primary efficacy end point was not met; however, CX\u20108998 improved some assessments of essential tremor, supporting further clinical investigation. \u00a9 2021 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28584","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T10:30:28Z","timestamp":1616668228000},"page":"1944-1949","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A Phase 2 Proof\u2010of\u2010Concept, Randomized, Placebo\u2010Controlled Trial of <scp>CX<\/scp>\u20108998 in Essential Tremor"],"prefix":"10.1002","volume":"36","author":[{"given":"Spyros","family":"Papapetropoulos","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey","family":"Versavel","sequence":"additional","affiliation":[{"name":"Cerevel Therapeutics, LLC  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Newbold","sequence":"additional","affiliation":[{"name":"Jazz Pharmaceuticals  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyder A.","family":"Jinnah","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh","family":"Pahwa","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly E.","family":"Lyons","sequence":"additional","affiliation":[{"name":"University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodger","family":"Elble","sequence":"additional","affiliation":[{"name":"Southern Illinois University School of Medicine  Springfield Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Ondo","sequence":"additional","affiliation":[{"name":"Houston Methodist Neurological Institute  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Zesiewicz","sequence":"additional","affiliation":[{"name":"University of South Florida Ataxia Research Center  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hedera","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Louisville  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Handforth","sequence":"additional","affiliation":[{"name":"VA Greater Los Angeles Healthcare System  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Elder","sequence":"additional","affiliation":[{"name":"PharPoint Research, Inc.  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