{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:11:06Z","timestamp":1782738666060,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>There remains uncertainty as to the optimal way to initiate therapy for Parkinson's disease (PD) to maximize benefit and minimize adversity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The objective was to determine if P2B001 (a fixed, low\u2010dose, extended\u2010release [ER] combination of pramipexole 0.6\u2009mg and rasagiline 0.75\u2009mg) is superior to each of its components and compare its safety and efficacy to optimized treatment with marketed doses of pramipexole\u2010ER.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a 12\u2010week, double\u2010blind study (NCT03329508). Total of 544 untreated patients with PD were randomized (2:2:2:1) to treatment with P2B001, its individual components (pramipexole\u2010ER 0.6\u2009mg or rasagiline\u2010ER 0.75\u2009mg), or commercial doses of pramipexole\u2010ER titrated to optimal dose (1.5\u20134.5\u2009mg). The primary endpoint was change from baseline to week 12 in Unified Parkinson's Disease Rating Scale (UPDRS) parts II\u2009and III. The key secondary endpoint was the change from baseline in the Epworth Sleepiness Scale (ESS) for P2B001 versus the titrated dose of pramipexole\u2010ER.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>P2B001 provided superior efficacy compared to each of its components; mean (95% CI) treatment differences in UPDRS II\u2009+\u2009III scores were \u22122.66 (95% CI, \u22124.33 to \u22121.00) versus pramipexole\u2010ER 0.6\u2009mg (<jats:italic>P<\/jats:italic>\u2009=\u20090.0018) and\u2009\u2212\u20093.30 (95% CI, \u22124.96 to \u22121.63) versus rasagiline\u2010ER 0.75\u2009mg (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). P2B001 had comparable efficacy with the titrated dose of pramipexole\u2010ER (mean, 3.2\u2009mg), but significantly less worsening in daytime\u2010sleepiness (ESS treatment difference: \u22122.66 [95% CI, \u22123.50 to \u22121.81]; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.0001). P2B001 was well\u2010tolerated with fewer sleep\u2010related and dopaminergic adverse events than titrated doses of pramipexole\u2010ER including somnolence, orthostatic hypotension, and neuropsychiatric side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>P2B001 had superior efficacy to its individual components and was comparable with commercially used doses of pramipexole\u2010ER with less worsening of sleepiness and fewer dopaminergic adverse events. These findings support considering once\u2010daily P2B001 as initial therapy for patients with early PD. \u00a9 2023 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29642","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T04:49:41Z","timestamp":1698382181000},"page":"350-359","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Randomized Phase 3 Study Comparing <scp>P2B001<\/scp> to its Components (Low\u2010Dose Extended\u2010Release Rasagiline and Pramipexole) and to Optimized Doses of Marketed Extended\u2010Release Pramipexole in Early Parkinson's Disease"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5471-1471","authenticated-orcid":false,"given":"C. Warren","family":"Olanow","sequence":"first","affiliation":[{"name":"Departments of Neurology and Department of Neuroscience, Mount Sinai School of Medicine  New York New York USA"},{"name":"Clintrex Research Corporation  Sarasota Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6369-1203","authenticated-orcid":false,"given":"Robert A.","family":"Hauser","sequence":"additional","affiliation":[{"name":"Department of Neurology, Parkinson Foundation Center of Excellence University of South Florida  Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Burdick","sequence":"additional","affiliation":[{"name":"Booth Gardner Parkinson's Care Center, Eastside Neuroscience Institute, Evergreen Health Medical Center  Kirkland WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Dhall","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy Antonelle","family":"de Marcaida","sequence":"additional","affiliation":[{"name":"Hartford HealthCare Chase Family Movement Disorders Center  Vernon Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon A.","family":"Gil","sequence":"additional","affiliation":[{"name":"Hartford HealthCare Chase Family Movement Disorders Center  Vernon Connecticut USA"},{"name":"Parkinson's Disease Treatment Center of SW Florida  Naples Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Kreitzman","sequence":"additional","affiliation":[{"name":"Movement Disorders Center of Long Island  Commack New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence W.","family":"Elmer","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Toledo College of 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