{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:10:32Z","timestamp":1790647832186,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The study's aim is to investigate the efficacy and safety of SOM3355 (bevantolol hydrochloride), a \u03b2<jats:sub>1<\/jats:sub>\u2010adrenoreceptor antagonist with recently identified vesicular monoamine transporter type 2 inhibitory properties, as a repositioned treatment to reduce chorea in Huntington's disease (HD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A randomized, placebo\u2010controlled proof\u2010of\u2010concept study was performed in 32 HD patients allocated to 2 arms of 4 sequential 6\u2010week periods each. Patients received placebo and SOM3355 at 100 and 200\u2009mg twice daily in a crossover design. The primary endpoint was improvement by at least 2 points in the total maximal chorea score in any active drug period compared with the placebo period.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The primary endpoint was met in 57.1% of the patients. Improvements \u22653, \u22654, \u22655 and \u22656 points <jats:italic>vs<\/jats:italic>. placebo treatment were observed in 28.6, 25.0, 17.9 and 10.7% of the patients, respectively. A mixed\u2010model analysis found a significant improvement in the total maximal chorea score of \u22121.14 (95% confidence interval, \u22122.11 to \u22120.16; <jats:italic>P<\/jats:italic>\u00a0=\u2009.0224) with 200\u2009mg twice daily SOM3355 treatment compared with placebo treatment. These results were paralleled by Clinical and Patient Global Impression of Change ratings (secondary endpoints). An elevation in plasma prolactin levels by 1.7\u20131.9\u2010fold was recorded (<jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.005), probably reflecting the effect on the dopamine pathway, consistent with vesicular monoamine transporter type 2 inhibition. The most frequent adverse events during SOM3355 administration were mild to moderate.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Within the limits of this study, the results suggest that SOM3355 reduces chorea in patients with HD and is well\u2010tolerated. Larger studies are necessary to confirm its therapeutic utility as an antichoreic drug.<\/jats:p><jats:p>EudraCT number: 2018\u2013000203\u201016 and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> Identifier: NCT03575676.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.15635","type":"journal-article","created":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T04:00:00Z","timestamp":1670644800000},"page":"1656-1664","source":"Crossref","is-referenced-by-count":12,"title":["A proof\u2010of\u2010concept study with SOM3355 (bevantolol hydrochloride) for reducing chorea in Huntington's disease"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-7486","authenticated-orcid":false,"given":"Josep","family":"Gamez","sequence":"first","affiliation":[{"name":"Neurology Department, GMA Clinic, European Reference Network on Rare Neurological Diseases (ERN\u2010RND) Autonomous University of Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6943-3707","authenticated-orcid":false,"given":"Matilde","family":"Calopa","sequence":"additional","affiliation":[{"name":"Movement Disorders Unit, Neurology Department Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9172-9694","authenticated-orcid":false,"given":"Esteban","family":"Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Parkinson's Disease and Movement Disorders Unit, Neurology Service, Institut Cl\u00ednic de Neuroci\u00e8ncies, Hospital Cl\u00ednic de Barcelona University of Barcelona  Barcelona Spain"},{"name":"European Reference Network for Rare Neurological Diseases (ERN\u2010RND)  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0080-2516","authenticated-orcid":false,"given":"Aileen","family":"Ferr\u00e9","sequence":"additional","affiliation":[{"name":"SOM Innovation Biotech SA  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Huertas","sequence":"additional","affiliation":[{"name":"SOM Innovation Biotech SA  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"McAllister","sequence":"additional","affiliation":[{"name":"Neurenable GmbH  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Reig","sequence":"additional","affiliation":[{"name":"SOM Innovation Biotech SA  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Scart\u2010Gr\u00e8s","sequence":"additional","affiliation":[{"name":"SOM Innovation Biotech SA  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6424-2784","authenticated-orcid":false,"given":"Ra\u00fal","family":"Insa","sequence":"additional","affiliation":[{"name":"SOM Innovation Biotech SA  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4870-1431","authenticated-orcid":false,"given":"Jaime","family":"Kulisevsky","sequence":"additional","affiliation":[{"name":"Movement Disorders Unit, Neurology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigaci\u00f3 Biom\u00e8dica Sant Pau Autonomous University of Barcelona  Barcelona Spain"},{"name":"Biomedical Research Networking Center on Neurodegenerative Diseases (CIBERNED)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nurt.2008.01.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13413"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4377-2369-4.00014-7"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750\u20101172\u20105\u201040"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(06)70494\u2010X"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2013.4408"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25996"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2016.02.008"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.0299"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000835"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737175.2015.1025383"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15543"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102019\u2010322038"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000198586.85250.13"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.8655"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.1986.tb04506.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010022\u201000956\u20108"},{"key":"e_1_2_10_20_1","unstructured":"AUSTEDO\u2122 (deutetrabenazine) tablets for oral use: highlights of prescribing information. Published online 2017.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/208082s000lbl.pdf"},{"key":"e_1_2_10_21_1","unstructured":"XENAZINE\u00ae (tetrabenazine) tablets for oral use: highlights of prescribing information. Published online 2017.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/021894s013lbl.pdf"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010017\u20100831\u20100"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.2020.18.2.322"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002\u20109149(86)90590\u20104"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495\u2010198835010\u201000001"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/000331978603700313"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/000331978603700318"},{"key":"e_1_2_10_28_1","unstructured":"Calvan\u00ae SmPC.;2010."},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527\u20103466.1985.tb00473.x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870110204"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002093\u2010199700112\u201000004"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300873"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3233\/JHD\u2010140115"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10111704"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15543"},{"key":"e_1_2_10_37_1","first-page":"251","volume-title":"Handbook of Clinical Neurology","author":"Vuong K","year":"2018"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00221"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00710"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.239160"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269216307087148"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/jne.12885"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3233\/JHD\u2010210493"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286\u2010020\u201000669\u20102"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.5334\/tohm.129"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1086\/302388"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010016\u20100670\u20104"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.24062"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15635","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcp.15635","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.15635","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T19:21:40Z","timestamp":1692300100000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.15635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,28]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1111\/bcp.15635"],"URL":"https:\/\/doi.org\/10.1111\/bcp.15635","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,28]]}}}