{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:03:24Z","timestamp":1791443004101,"version":"4.3.3"},"reference-count":11,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,7,24]],"date-time":"2016-07-24T00:00:00Z","timestamp":1469318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2016,11]]},"abstract":"Aims<\/jats:title>To prospectively select the dose of the paliperidone palmitate 3\u2010month (PP3M) formulation, using a pharmacometric bridging strategy based on the paliperidone palmitate 1\u2010month (PP1M) formulation previously approved for schizophrenia treatment.<\/jats:p><\/jats:sec>Methods<\/jats:title>Pharmacokinetic (PK) data from a 6\u2010month interim analysis of a single dose PP3M Phase I clinical trial was integrated with a previously developed PP1M population\u2010PK model. The model was updated to incorporate formulation as a covariate on absorption parameters and to explore the most critical design element of the Phase III study: the PP1M\u2010to\u2010PP3M dose multiplier for patients switching formulations. Plasma paliperidone concentrations were measured at predetermined intervals during Phase III, enabling comparison of the multiple\u2010dose PK between PP1M and PP3M. Exposure matching was assessed graphically to determine whether paliperidone plasma concentrations from the two formulations overlapped.<\/jats:p><\/jats:sec>Results<\/jats:title>Prospective steady\u2010state PK simulations revealed that a 3.5 multiple of the PP1M dose would yield a corresponding PP3M dose with comparable exposure. The prospective pharmacometric simulation and observed Phase III PK data agreed closely. Phase III results confirmed the hypothesis that efficacy of PP3M was noninferior to that of PP1M. The similarity in exposures between the two formulations was likely a key determinant of the equivalent efficacy between the two products observed in the Phase III study.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Successful prospective PP3M Phase III clinical trial dose selection was achieved through the use of pharmacometric bridging, without conducting a Phase II study and using only limited Phase I data for PP3M. We estimate that this strategy reduced development time by 3\u20135 years and may be applicable to other drug development projects.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13050","type":"journal-article","created":{"date-parts":[[2016,6,22]],"date-time":"2016-06-22T23:00:01Z","timestamp":1466636401000},"page":"1364-1370","source":"Crossref","is-referenced-by-count":13,"title":["Prospective dose selection and acceleration of paliperidone palmitate 3\u2010month formulation development using a pharmacometric bridging strategy"],"prefix":"10.1111","volume":"82","author":[{"given":"Mahesh N.","family":"Samtani","sequence":"first","affiliation":[{"name":"Janssen Research & Development LLC New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha","family":"Nandy","sequence":"additional","affiliation":[{"name":"Janssen Research & Development LLC New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulien","family":"Ravenstijn","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, a Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Remmerie","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, a Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Vermeulen","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, a Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Russu","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, a Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"D'hoore","sequence":"additional","affiliation":[{"name":"Janssen Research & Development, a Division of Janssen Pharmaceutica NV Beerse Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen Z.","family":"Baum","sequence":"additional","affiliation":[{"name":"Janssen Research & Development LLC New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Savitz","sequence":"additional","affiliation":[{"name":"Janssen Research & Development LLC New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srihari","family":"Gopal","sequence":"additional","affiliation":[{"name":"Janssen Research & Development LLC New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Hough","sequence":"additional","affiliation":[{"name":"Janssen Research & Development LLC New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100235"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2165\/11316870-000000000-00000"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.597"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145709990988"},{"key":"e_1_2_9_6_1","first-page":"829","article-title":"Dosing and switching strategies for paliperidone palmitate: based on population pharmacokinetic modelling and clinical trial data","volume":"25","author":"Samtani MN","year":"2011","journal-title":"CNS Drugs"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.295"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2015.0241"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyw018"},{"key":"e_1_2_9_10_1","first-page":"25","article-title":"Management of antipsychotic treatment discontinuation and interruptions using model\u2010based simulations","volume":"4","author":"Samtani MN","year":"2012","journal-title":"Clin Pharmacol"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1185\/03007990903482772"},{"key":"e_1_2_9_12_1","unstructured":"MagnussonMO SamtaniMN PlanEL JonssonEN RossenuS VermeulenA.Population pharmacokinetic modeling of paliperidone palmitate 3\u2010month formulation. PAGE. Abstracts of the Annual Meeting of the Population Approach Group in Europe. Available athttp:\/\/www.page\u2010meeting.org\/?abstract=3408(last accessed 8 July 2016)."}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbcp.13050","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcp.13050","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T13:18:36Z","timestamp":1694611116000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bcp.13050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,24]]},"references-count":11,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,11]]}},"alternative-id":["10.1111\/bcp.13050"],"URL":"https:\/\/doi.org\/10.1111\/bcp.13050","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,24]]}}}