{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:31:02Z","timestamp":1790094662281,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"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":[[2022,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Inhalation of apomorphine could be a faster\u2010acting and more user\u2010friendly alternative to subcutaneous injection for treating\n off<\/jats:italic>\n periods in Parkinson's disease (PD).\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n The aim of this study was to compare the safety and pharmacokinetics of inhaled apomorphine (AZ\u2010009) with subcutaneous apomorphine (APO\u2010go PEN) in healthy volunteers (HVs) and to examine the safety, pharmacokinetics, and efficacy of AZ\u2010009 in patients with PD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In part A of this study, eight HVs received 1\u2009mg AZ\u2010009 and 2\u2009mg subcutaneous apomorphine in a randomized crossover manner. In the subsequent single ascending dose parts in HVs (part B, n\u00a0=\u00a016) and patients with PD (part C, n\u00a0=\u00a025), participants were randomized to placebo or AZ\u2010009 up to 4\u2009mg. In patients, after medication withdrawal, Movement Disorder Society\u2010Unified Parkinson's Disease Rating Scale part III and\n on\/off<\/jats:italic>\n states were assessed predose and postdose.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n AZ\u2010009 was rapidly absorbed with peak plasma concentrations at 2\u00a0minutes, as compared to 30 minutes for subcutaneous apomorphine. Adverse events for AZ\u2010009 were comparable to subcutaneous apomorphine, except for mild and transient throat irritation. Adverse events limited AZ\u2010009 dose escalation in HVs to 3\u00a0mg. Patients tolerated up to 4\u00a0mg. In patients with PD, 2, 3, and 4\u00a0mg AZ\u2010009 reduced mean Movement Disorder Society\u2010Unified Parkinson's Disease Rating Scale part III score (standard deviation) by 10.7 (13.6), 12.8 (7.9), and 10.3 (3.7) points, respectively, compared to 4.8 (4.9) after placebo at 10\u00a0minutes postdose. The percentage of patients achieving full\n on<\/jats:italic>\n within 45\u00a0minutes postdose increased dose dependently: 0% (placebo), 17% (2\u00a0mg), 50% (3\u00a0mg), and 83% (4\u00a0mg).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n AZ\u2010009 appears to be a rapid\u2010acting and reasonably well\u2010tolerated formulation for treating\n off<\/jats:italic>\n periods. \u00a9 2022 The Authors.\n Movement Disorders<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.28926","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T03:09:29Z","timestamp":1642648169000},"page":"790-798","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A Randomized Trial Assessing the Safety, Pharmacokinetics, and Efficacy During Morning\n \n Off<\/i>\n <\/scp>\n of\n AZ<\/scp>\n \u2010009"],"prefix":"10.1002","volume":"37","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":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-7978","authenticated-orcid":false,"given":"Jonas","family":"den Heijer","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research (CHDR) Leiden the Netherlands"},{"name":"Leiden University Medical Centre (LUMC) Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Puibert","sequence":"additional","affiliation":[{"name":"Ferrer Barcelona 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