{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T14:54:29Z","timestamp":1783090469676,"version":"3.54.6"},"reference-count":36,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPD"],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:p>Background: Current drug treatments have little efficacy in advanced-to-end-stage Parkinson\u2019s disease (advPD), yet there are no reports of interventional trials in advPD. D1 dopamine agonists have the potential to provide benefit. Objective: To determine the feasibility and safety of the selective D1\/D5 dopamine partial agonist PF 06412562 in advPD. Methods: A two-week, randomized, double blind, crossover phase Ib study in advPD patients compared standard-of-care (SoC) carbidopa\/levodopa with PF 06412562. Each week, there was a Day 1 baseline evaluation with overnight levodopa washout, then treatment on Days 2 and 3 with either SoC or PF-06412562 (split dose 25\u200a+\u200a20\u200amg), followed by discharge on Day 4. Primary endpoints were safety and tolerability. Secondary endpoints were global clinical impression of change (GCI-C) rated by clinicians and caregivers. Results: Eight advPD patients and their caregivers consented to participate and six were randomized (average disease duration: 22\u200ay). None withdrew voluntarily. One participant with baseline Day 1 dehydration, pre-renal kidney injury, and autonomic dysfunction experienced symptomatic and serious hypotension after receiving PF-06412562 in Week 1 and was discontinued from the study. All other adverse events were rated mild (PF-06412562: n\u200a=\u200a1, SoC: n\u200a=\u200a0), moderate (PF-06412562: n\u200a=\u200a1, SoC: n\u200a=\u200a1), or severe but non-serious (PF-06412562: n\u200a=\u200a3, SoC: n\u200a=\u200a2). No clinically meaningful laboratory changes were observed. Among the five participants who completed the study, GCI-C favored PF-06412562 in two per clinicians\u2019 and four participants per caregivers\u2019 rating. Conclusion: PF-06412562 was tolerated in advPD patients. This study provides the feasibility for future safety and efficacy studies in this population with unmet needs.<\/jats:p>","DOI":"10.3233\/jpd-202188","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T19:20:28Z","timestamp":1600802428000},"page":"1515-1527","source":"Crossref","is-referenced-by-count":21,"title":["The D1\/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson\u2019s Disease: A Feasibility Study"],"prefix":"10.1177","volume":"10","author":[{"given":"Xuemei","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Radiology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Neurosurgery, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Kinesiology, Penn State University, University Park, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mechelle M.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Neurology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Translational Brain Research Center, Penn State Hershey Medical Center, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Jodi","family":"Van Scoy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Humanities, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Psychiatry, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sol","family":"De Jesus","sequence":"additional","affiliation":[{"name":"Department of Neurology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Translational Brain Research Center, Penn State Hershey Medical Center, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Eslinger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Radiology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Medicine, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Arnold","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Fernandez-Mendoza","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethany","family":"Snyder","sequence":"additional","affiliation":[{"name":"Department of Neurology, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Harrington","sequence":"additional","affiliation":[{"name":"Department of Neurology, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxiao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marielle","family":"Delnomdedieu","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Duvvuri","sequence":"additional","affiliation":[{"name":"Cerevel Neurosciences LLC., Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan E.","family":"Mahoney","sequence":"additional","affiliation":[{"name":"Pfizer Inc., Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Gray","sequence":"additional","affiliation":[{"name":"Cerevel Neurosciences LLC., Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Mailman","sequence":"additional","affiliation":[{"name":"Department of Neurology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA"},{"name":"Translational Brain Research Center, Penn State Hershey Medical Center, Hershey, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JPD-202188_ref1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1212\/WNL.0000000000002509","article-title":"Levodopa therapy for Parkinson disease: A look backward and forward.S","volume":"86","author":"LeWitt","year":"2016","journal-title":"Neurology"},{"key":"10.3233\/JPD-202188_ref2","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1468-1331.2009.02900.x","article-title":"Neurotransmission in Parkinson\u2019s disease: Beyond dopamine","volume":"17","author":"Barone","year":"2010","journal-title":"Eur J Neurol"},{"key":"10.3233\/JPD-202188_ref3","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1002\/mdc3.12133","article-title":"Survey of health care workers suggests unmet palliative care needs in Parkinson\u2019s disease","volume":"2","author":"Fox","year":"2015","journal-title":"Mov Disord Clin Pract"},{"key":"10.3233\/JPD-202188_ref4","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.3389\/fneur.2018.01068","article-title":"A pilgrim\u2019s journey-when Parkinson\u2019s disease comes to an end in nursing homes","volume":"9","author":"Lex","year":"2018","journal-title":"Front Neurol"},{"key":"10.3233\/JPD-202188_ref5","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1124\/jpet.102.039867","article-title":"Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. I. A multivariate analysis of the binding profiles of 14 drugs at 21 native and cloned human receptor subtypes","volume":"303","author":"Millan","year":"2002","journal-title":"J Pharmacol Exp Therap"},{"key":"10.3233\/JPD-202188_ref6","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0072-9752(07)83004-1","article-title":"Dopamine receptor pharmacology","volume":"83","author":"Mailman","year":"2007","journal-title":"Handb Clin Neurol"},{"key":"10.3233\/JPD-202188_ref7","first-page":"480260","article-title":"Treatment of advanced Parkinson\u2019s disease","volume":"2010","author":"Varanese","year":"2011","journal-title":"Parkinsons Dis"},{"key":"10.3233\/JPD-202188_ref8","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s40266-018-0629-0","article-title":"Factors to consider in the selection of dopamine agonists for older persons with Parkinson\u2019s disease","volume":"36","author":"Latt","year":"2019","journal-title":"Drugs Aging"},{"key":"10.3233\/JPD-202188_ref9","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1002\/1531-8257(200007)15:4<664::AID-MDS1010>3.0.CO;2-D","article-title":"The use of dopamine agonists in very elderly patients with Parkinson\u2019s disease","volume":"15","author":"Shulman","year":"2000","journal-title":"Mov Disord"},{"key":"10.3233\/JPD-202188_ref10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0074-7742(01)48014-7","article-title":"D1 dopamine receptors","volume":"48","author":"Huang","year":"2001","journal-title":"Int Rev Neurobiol"},{"key":"10.3233\/JPD-202188_ref11","first-page":"255","article-title":"Dopamine D1 receptor agonists as antiparkinson drugs","volume":"19","author":"Mailman","year":"1998","journal-title":"Trends Pharmacol Sci"},{"key":"10.3233\/JPD-202188_ref12","first-page":"1582","article-title":"Parkinson\u2019s disease and D1 dopamine receptors","volume":"2","author":"Mailman","year":"2001","journal-title":"Curr Opin Investig Drugs"},{"key":"10.3233\/JPD-202188_ref13","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/0014-2999(91)90508-N","article-title":"Dihydrexidine, a full dopamine D1 agonist, reduces MPTP-induced parkinsonism in monkeys","volume":"199","author":"Taylor","year":"1991","journal-title":"Eur J Pharmacol"},{"key":"10.3233\/JPD-202188_ref14","doi-asserted-by":"crossref","first-page":"3445","DOI":"10.1021\/jm00018a002","article-title":"(5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopent-1- ena[c]-phenanthrene-9,10-diol (A-86929): A potent and selective dopamine D1 agonist that maintains behavioral efficacy following repeated administration and characterization of its diacetyl prodrug (ABT-431)","volume":"38","author":"Michaelides","year":"1995","journal-title":"J Med Chem"},{"key":"10.3233\/JPD-202188_ref15","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/1531-8249(199906)45:6<736::AID-ANA7>3.0.CO;2-F","article-title":"ABT-431, a D1 receptor agonist prodrug, has efficacy in Parkinson\u2019s disease","volume":"45","author":"Rascol","year":"1999","journal-title":"Ann Neurol"},{"key":"10.3233\/JPD-202188_ref16","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1001\/archneur.58.2.249","article-title":"Induction by dopamine D1 receptor agonist ABT-431 of dyskinesia similar to levodopa in patients with Parkinson disease","volume":"58","author":"Rascol","year":"2001","journal-title":"Arch Neurol"},{"key":"10.3233\/JPD-202188_ref17","doi-asserted-by":"crossref","first-page":"11384","DOI":"10.1021\/acs.jmedchem.8b01622","article-title":"Discovery and lead optimization of atropisomer D1 agonists with reduced desensitization","volume":"61","author":"Davoren","year":"2018","journal-title":"J Med Chem"},{"key":"10.3233\/JPD-202188_ref18","first-page":"714","article-title":"D-1 dopamine receptor agonists are more effective in alleviating advanced than mild parkinsonism in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys","volume":"292","author":"Goulet","year":"2000","journal-title":"J Pharmacol Exp Therap"},{"key":"10.3233\/JPD-202188_ref20","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/s41467-017-02776-7","article-title":"Impaired beta-arrestin recruitment and reduced desensitization by non-catechol agonists of the D1 dopamine receptor","volume":"9","author":"Gray","year":"2018","journal-title":"Nat Commun"},{"key":"10.3233\/JPD-202188_ref21","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s40120-018-0114-z","article-title":"Phase 1 Parkinson\u2019s disease studies show the dopamine D1\/D5 agonist PF-06649751 is safe and well tolerated","volume":"7","author":"Sohur","year":"2018","journal-title":"Neurol Ther"},{"key":"10.3233\/JPD-202188_ref22","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1159\/000492498","article-title":"Evaluation of D1\/D5 partial agonist PF-06412562 in Parkinson\u2019s disease following oral administration","volume":"18","author":"Papapetropoulos","year":"2018","journal-title":"Neurodegener Dis"},{"key":"10.3233\/JPD-202188_ref23","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1093\/brain\/awf080","article-title":"The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service","volume":"125","author":"Hughes","year":"2002","journal-title":"Brain"},{"key":"10.3233\/JPD-202188_ref24","first-page":"339","article-title":"Effects of the full dopamine D1 receptor agonist dihydrexidine in Parkinson\u2019s disease","volume":"21","author":"Blanchet","year":"1998","journal-title":"Clin Neuropharmacol"},{"key":"10.3233\/JPD-202188_ref25","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1161\/HYPERTENSIONAHA.115.06617","article-title":"Mineralocorticoid receptor activation contributes to the supine hypertension of autonomic failure","volume":"67","author":"Arnold","year":"2016","journal-title":"Hypertension"},{"key":"10.3233\/JPD-202188_ref26","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1172\/JCI109897","article-title":"Suppressor cell regulation of cell-mediated immune responses in renal infection in vitro modulation of suppressor cell activity","volume":"66","author":"Miller","year":"1980","journal-title":"J Clin Invest"},{"key":"10.3233\/JPD-202188_ref27","doi-asserted-by":"crossref","first-page":"e76595","DOI":"10.1371\/journal.pone.0076595","article-title":"The nature of progression in Parkinson\u2019s disease: An application of non-linear, multivariate, longitudinal random effects modelling","volume":"8","author":"Kuramoto","year":"2013","journal-title":"PLoS One"},{"key":"10.3233\/JPD-202188_ref28","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1001\/jamaneurol.2017.0985","article-title":"Conversion to Parkinson disease in the PARS hyposmic and dopamine transporter-deficit prodromal cohort","volume":"74","author":"Jennings","year":"2017","journal-title":"JAMA Neurol"},{"key":"10.3233\/JPD-202188_ref29","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1111\/ene.13397","article-title":"Progression of prodromal motor and non-motor symptoms in the premotor phase study - 2-year follow-up data","volume":"24","author":"Liepelt-Scarfone","year":"2017","journal-title":"Eur J Neurol"},{"key":"10.3233\/JPD-202188_ref30","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1136\/jnnp-2014-308786","article-title":"Parkinson\u2019s disease beyond 20 years","volume":"86","author":"Cilia","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"10.3233\/JPD-202188_ref31","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1472-684X-11-20","article-title":"Clinical aspects of palliative care in advanced Parkinson\u2019s disease","volume":"11","author":"Lokk","year":"2012","journal-title":"BMC Palliat Care"},{"key":"10.3233\/JPD-202188_ref32","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S0895-7061(99)00059-X","article-title":"Fenoldopam: A new parenteral antihypertensive: Consensus roundtable on the management of perioperative hypertension and hypertensive crises","volume":"12","author":"Oparil","year":"1999","journal-title":"Am J Hypertens"},{"key":"10.3233\/JPD-202188_ref33","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1553-2712.2000.tb02039.x","article-title":"Fenoldopam, a dopamine agonist, for hypertensive emergency: A multicenter randomized trial. Fenoldopam Study Group","volume":"7","author":"Tumlin","year":"2000","journal-title":"Acad Emerg Med"},{"key":"10.3233\/JPD-202188_ref34","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.schres.2007.03.011","article-title":"A single 20 mg dose of dihydrexidine (DAR-0100), a full dopamine D1 agonist, is safe and tolerated in patients with schizophrenia","volume":"93","author":"George","year":"2007","journal-title":"Schizophr Res"},{"key":"10.3233\/JPD-202188_ref35","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/npp.2014.192","article-title":"Effects of the D1 dopamine receptor agonist dihydrexidine (DAR-0100A) on working memory in schizotypal personality disorder","volume":"40","author":"Rosell","year":"2015","journal-title":"Neuropsychopharmacology"},{"key":"10.3233\/JPD-202188_ref36","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.schres.2007.03.033","article-title":"A single 20 mg dose of the full D1 dopamine agonist dihydrexidine (DAR-0100) increases prefrontal perfusion in schizophrenia","volume":"94","author":"Mu","year":"2007","journal-title":"Schizophr Res"},{"key":"10.3233\/JPD-202188_ref37","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1097\/00005344-198407000-00005","article-title":"The dopamine agonist bromocriptine induces hypotension by venous and arteriolar dilation","volume":"6","author":"Johns","year":"1984","journal-title":"J Cardiovasc Pharmacol"}],"container-title":["Journal of Parkinson's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JPD-202188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:48:49Z","timestamp":1777610929000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JPD-202188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,27]]},"references-count":36,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3233\/jpd-202188","relation":{},"ISSN":["1877-7171","1877-718X"],"issn-type":[{"value":"1877-7171","type":"print"},{"value":"1877-718X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,27]]}}}