{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:21:35Z","timestamp":1790299295828,"version":"4.1.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100009655","name":"Sunovion","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009655","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bial \u2013 Portela & C"},{"name":"Universit\u00e4tsklinikum Ulm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Apomorphine sublingual film (SL-APO) is an on-demand treatment for OFF episodes in patients with Parkinson\u2019s disease (PD).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To assess the long-term (\u2265\u20093\u00a0years) safety\/tolerability and efficacy of SL-APO.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Study CTH-301 (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link> NCT02542696; registered 2015-09-03) was a phase 3, multicentre, open-label study of SL-APO in PD patients with motor fluctuations, comprised of a dose-titration and long-term safety phase. All participants received SL-APO. The primary endpoint was safety\/tolerability (treatment-emergent adverse events [TEAEs]) during the long-term safety phase. Efficacy assessments included the Movement Disorder Society-Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS) part III (motor examination), assessed at weeks 24, 36 and 48 during the first year of the long-term safety phase.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>496 patients were included and 120 (24.2%) completed the long-term safety phase. Mean duration of SL-APO exposure was 294.3\u00a0days. TEAEs related to study drug were experienced by 65.3% of patients (most common: nausea [6.0%], stomatitis [1.8%], lip swelling [1.8%], dizziness [1.6%], oral mucosal erythema [1.6%], mouth ulceration [1.6%]). TEAEs leading to study drug withdrawal were experienced by 34.0% of patients (most common: nausea [5.4%], lip swelling [4.5%], mouth ulceration [2.6%], stomatitis [2.3%]). A clinically meaningful reduction in MDS-UPDRS part III score was observed as soon as 15\u00a0min following administration of SL-APO, with peak effects observed approximately 30\u00a0min post-dose and sustained up to 90\u00a0min post-dose; results were consistent over 48\u00a0weeks.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>SL-APO was generally well tolerated and efficacious over the long term as an on-demand treatment for OFF episodes in patients with PD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-024-12323-2","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T07:02:00Z","timestamp":1711609320000},"page":"3554-3570","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Long-term safety, tolerability and efficacy of apomorphine sublingual film in patients with Parkinson\u2019s disease complicated by OFF episodes: a phase 3, open-label study"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7106-9270","authenticated-orcid":false,"given":"Jan","family":"Kassubek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0449-973X","authenticated-orcid":false,"given":"Stewart A.","family":"Factor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9258-1735","authenticated-orcid":false,"given":"Ernest","family":"Balaguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8314-5573","authenticated-orcid":false,"given":"Johannes","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2815-0505","authenticated-orcid":false,"given":"K. 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Expert Rev Neurother 21(2):169\u2013177. https:\/\/doi.org\/10.1080\/14737175.2020.1855145","journal-title":"Expert Rev Neurother"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-024-12323-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-024-12323-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-024-12323-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,29]],"date-time":"2024-05-29T15:15:15Z","timestamp":1716995715000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-024-12323-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,28]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["12323"],"URL":"https:\/\/doi.org\/10.1007\/s00415-024-12323-2","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,28]]},"assertion":[{"value":"3 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 March 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Jan Kassubek has received honoraria or consultation fees from AbbVie, Bial, Biogen, Desitin, Esteve, Licher MT, Medtronic, NeuroDerm, Novartis, STADA, UCB Pharma, and Zambon; in addition, he is Specialty Chief Editor for <i>Frontiers in Neurology<\/i> (section Applied Neuroimaging) and Associate Editor (Neurology) for <i>Therapeutic Advances in Chronic Disease<\/i>. Stewart A. Factor has received honoraria from Lundbeck, Biogen, and Takeda; grants from Medtronic, Boston Scientific, Sun Pharmaceuticals Advanced Research Company, Aspen, Biohaven, Neurocrine, Voyager, Prilenia Therapeutics, CHDI Foundation, Michael J. Fox Foundation, NIH 1 P50 NS123103-01, NIH 1R01NS125294-01, and Parkinson Foundation; royalties from Demos, Blackwell Futura, Springer for textbooks, and UpToDate; and other support from Cronos. Ernest Balaguer is Director of Research at Hospital Universitari General de Catalunya and signs agreements with the hospital to perform clinical trials. Johannes Schwarz received honoraria in the past 5\u00a0years from UCB, BIAL and AbbVie for presentations and consulting. K. Ray Chaudhuri has received funding from Parkinson\u2019s UK, NIHR, UCB, and the European Union; he received honoraria from UCB, Abbott, Britannia, US Worldmeds, and Otsuka Pharmaceuticals; and acted as a consultant for AbbVie, UCB, and Britannia. Stuart H. Isaacson reports honoraria for CME, consultancy, research grants, and\/or promotional speaker work on behalf of AbbVie, Acadia Pharmaceuticals Inc., Acorda Therapeutics Inc., Adamas Pharmaceuticals Inc., Addex Therapeutics, AFFiRiS AG, Alexza Pharmaceuticals, Allergan, Amarantus BioScience, Amneal Pharmaceuticals, Aptinyx, Axial Therapeutics Inc., Axovant Gene Therapies, BenevolentAI, Biogen, Britannia Pharmaceuticals, Cadent Therapeutics, Cala Health, Cerecor Inc., Cerevel Therapeutics, Cipla, Eli Lilly, Enterin Inc., GE HealthCare, Global Kinetics Pty Ltd., Impax Laboratories, Impel NeuroPharma, Intec Pharma, Ipsen, Jazz Pharmaceuticals, Kyowa Kirin, Lundbeck, Merz Pharmaceuticals, Michael J. Fox Foundation, Mitsubishi Tanabe Pharma, Neuraly, Neurocrine Biosciences, NeuroDerm, Parkinson Study Group, Pharma Two B, Prilenia Therapeutics, Promentis Pharmaceuticals Inc., Revance, Roche, Sanofi, Sunovion Pharmaceuticals Inc., Sun Pharma, Supernus Pharmaceuticals Inc., Teva Pharmaceuticals, Theravance Biopharma, and UCB. Stacy Wu is an employee of Sumitomo Pharma America Inc. Carmen Denecke Muhr is an employee of Bial-Portela & C\u00aa. Jaime Kulisevsky has received consulting fees from Roche and Zambon; honoraria from Zambon, Teva, Bial, UCB; research funding from Roche, Zambon, Ciberned; Instituto de Salud Carlos III; Fundaci\u00f3 La Marat\u00f3 de TV3.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice Guidance, the ethical principles that had their origin in the Declaration of Helsinki, and all applicable local law(s) and regulation(s). In accordance with ICH guidance, the protocol (including the final version of the patient informed consent form) was approved by the Institutional Review Board (IRB)\/Independent Ethics Committee (IEC) before any patients were enrolled (see Supplementary Information for details of central IRBs\/IECs).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"All patients provided written informed consent prior to participation in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}