{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:57:58Z","timestamp":1774580278982,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Apomorphine, used to treat <jats:italic>OFF<\/jats:italic> episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal solution could offer a non\u2010invasive and user\u2010friendly alternative. This two\u2010part clinical study evaluated the safety, tolerability, pharmacokinetics (PK), and dose proportionality of a novel apomorphine hydrochloride oromucosal solution, as well as its relative bioavailability to subcutaneous apomorphine injection and apomorphine sublingual film. In part A of the study, 12 patients with PD received 2\u2009mg oromucosal apomorphine (4% weight\/volume) and 2\u2009mg subcutaneous apomorphine in a randomized order, followed by 4 and 8\u2009mg oromucosal apomorphine. In part B of the study, 13 patients with PD received 7\u2009mg oromucosal apomorphine (7% weight\/volume) and 30\u2009mg sublingual apomorphine in a randomized order, followed by 14\u2009mg oromucosal apomorphine. Washout between dose administrations in both study parts was at least 2\u2009days. Safety, tolerability, and PK were assessed pre\u2010 and post\u2010dose. Both study parts showed that oromucosal apomorphine was generally well\u2010tolerated. Observed side effects were typical for apomorphine administration and included asymptomatic orthostatic hypotension, yawning, fatigue, and somnolence. Oromucosal apomorphine exposure increased with dose, although less than dose proportional. The mean (SD) maximum exposure reached with 14\u2009mg oromucosal apomorphine was 753.0 (298.6) ng*min\/mL (area under the plasma concentration\u2013time curve from zero to infinity) and 8.0 (3.3) ng\/mL (maximum plasma concentration). This was comparable to exposure reached after 2\u2009mg subcutaneous apomorphine and approximately half of the exposure observed with 30\u2009mg sublingual apomorphine. In summary, clinically relevant plasma concentrations could be reached in PD patients without tolerability issues.<\/jats:p>","DOI":"10.1111\/cts.13796","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T10:48:32Z","timestamp":1715078912000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical trial evaluating apomorphine oromucosal solution in Parkinson's disease patients"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3907-072X","authenticated-orcid":false,"given":"Eva","family":"Thijssen","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research (CHDR)  Leiden The Netherlands"},{"name":"Leiden University Medical Centre (LUMC)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-666X","authenticated-orcid":false,"given":"Bert","family":"Tuk","sequence":"additional","affiliation":[{"name":"Criceto IKM  Casteren The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3098-5619","authenticated-orcid":false,"given":"Michel","family":"Cakici","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research (CHDR)  Leiden The Netherlands"},{"name":"Leiden University Medical Centre (LUMC)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veerle","family":"van Velze","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research (CHDR)  Leiden The Netherlands"},{"name":"Leiden University Medical Centre (LUMC)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0089-1846","authenticated-orcid":false,"given":"Erica","family":"Klaassen","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research (CHDR)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frans","family":"Merkus","sequence":"additional","affiliation":[{"name":"Innotesto BV  Kasterlee Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5088-480X","authenticated-orcid":false,"given":"Teus","family":"van Laar","sequence":"additional","affiliation":[{"name":"Groningen University Medical Center (UMCG)  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0483-841X","authenticated-orcid":false,"given":"Philip","family":"Kremer","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research (CHDR)  Leiden The Netherlands"},{"name":"Leiden University Medical Centre (LUMC)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4655-6667","authenticated-orcid":false,"given":"Geert Jan","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research (CHDR)  Leiden The Netherlands"},{"name":"Leiden University Medical Centre (LUMC)  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/S40268-018-0230-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JPBA.2020.113493"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/MDC3.12915"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ENE.12091"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ANE.12107"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/MDS.870130505"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCONREL.2004.09.011"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/MDS.28926"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/MDS.870060304"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.EJPB.2011.01.024"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410260209"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2016.11.017"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/MDS.1069"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.PARKRELDIS.2007.07.013"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/S40120-021-00251-6"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/CTS.13008"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1026451721686"},{"key":"e_1_2_10_19_1","unstructured":"APO\u2010go Pen 10mg\/ml Solution for Injection \u2010 Summary of Product Characteristics (SmPC) \u2010 (emc). 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