{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:20:25Z","timestamp":1792840825787,"version":"4.5.0"},"reference-count":14,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Valbenazine improved chorea in individuals with Huntington's disease compared to placebo in a phase 3, placebo\u2010controlled study (KINECT\u2010HD). Population pharmacokinetics (PK) and exposure\u2013response (E\u2013R) analyses focused on understanding the PK characteristics of valbenazine and its active metabolite, [+]\u2010\u03b1\u2010dihydrotetrabenazine ([+]\u2010\u03b1\u2010HTBZ), and their correlation with clinical efficacy measured by the total maximal chorea (TMC) score. Consistent with previous analyses, a two\u2010compartmental population PK model adequately described valbenazine and [+]\u2010\u03b1\u2010HTBZ plasma disposition, generating reliable individual\u2010predicted exposure levels for sequential E\u2013R analysis. The distributions of individual\u2010predicted steady\u2010state exposures of valbenazine and [+]\u2010\u03b1\u2010HTBZ were found to largely overlap between patients with tardive dyskinesia and those with Huntington's disease (HD) chorea. The relationship between the change from baseline in TMC score and [+]\u2010\u03b1\u2010HTBZ systemic exposure were effectively characterized by a nonlinear E\n                    <jats:sub>max<\/jats:sub>\n                    model, with negligible impact from selected covariates. The predicted E\u2013R curve closely aligns with the observed data, exhibiting a negative slope that indicates an increasing clinical response with escalating doses of 40, 60, and 80 mg\/day. Predicted efficacy appears to reach a plateau at 80 mg once daily (QD), suggesting minimal additional benefit beyond this dosage. Together, results from the population PK model and E\u2013R analyses reinforce the evidence base for valbenazine efficacy in reducing chorea severity, as demonstrated by the notable decrease in TMC scores compared to baseline. They also endorse the selection of dosing regimens ranging from 40 to 80 mg QD for the treatment of chorea in patients with HD.\n                  <\/jats:p>","DOI":"10.1002\/jcph.70092","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T02:55:58Z","timestamp":1755053758000},"page":"1777-1788","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Population Pharmacokinetic and Exposure\u2010Efficacy Analyses of Valbenazine in Patients with Huntington's Disease: Supporting Dose Selection for Chorea Management"],"prefix":"10.1002","volume":"65","author":[{"given":"Hoa Q.","family":"Nguyen","sequence":"first","affiliation":[{"name":"Neurocrine Biosciences  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan L.","family":"Crass","sequence":"additional","affiliation":[{"name":"Ann Arbor Pharmacometrics Group  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunny","family":"Chapel","sequence":"additional","affiliation":[{"name":"Ann Arbor Pharmacometrics Group  Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Yi Steve","family":"Kuan","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gordon","family":"Loewen","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satjit","family":"Brar","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"A Physician's Guide to the Management of Huntington's Disease","author":"Nance M","year":"2011"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00127-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.239160"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1205"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2498"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9282-9"},{"key":"e_1_2_10_8_1","volume-title":"Guidance for Industry: Exposure\u2010Response Relationships \u2014 Study Design, Data Analysis, and Regulatory Applications","author":"US Food and Drug Administration","year":"2003"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12015"},{"issue":"15","key":"e_1_2_10_10_1","article-title":"Effect of paroxetine on the pharmacokinetics of valbenazine and its active metabolite [abstract]","volume":"94","author":"Sm","year":"2020","journal-title":"Neurology"},{"issue":"30","key":"e_1_2_10_11_1","first-page":"S167","article-title":"A minimal clinically important difference for UHDRS\u00ae total maximal chorea score as a measure of chorea severity in Huntington disease [abstract]","volume":"94","author":"Furr Stimming E","year":"2023","journal-title":"Ann Neurol"},{"issue":"10","key":"e_1_2_10_12_1","first-page":"S666","article-title":"Somnolence\u2010related events over time with valbenazine treatment for chorea associated with Huntington's disease [abstract]","volume":"11","author":"Furr Stimming E","year":"2024","journal-title":"Mov Disord"},{"key":"e_1_2_10_13_1","unstructured":"INGREZZA\u00aecapsules and INGREZZA\u00aeSPRINKLE capsules. Prescribing information.Neurocrine Biosciences Inc.2025. Accessed June 25 2025.https:\/\/www.ingrezza.com\/tardive\u2010dyskinesia\/view\u2010pi"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/02698811241248391"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/S109285292000108X"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70092","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70092","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70092","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:07:07Z","timestamp":1772982427000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70092"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,12]]},"references-count":14,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1002\/jcph.70092"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70092","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,12]]},"assertion":[{"value":"2025-04-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}