{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T08:44:35Z","timestamp":1762245875268,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    TAK\u2010071 is a novel muscarinic M\n                    <jats:sub>1<\/jats:sub>\n                    positive allosteric modulator under investigation for the treatment of cognitive impairment and falls associated with Parkinson disease (PD). This study evaluated population pharmacokinetics of TAK\u2010071 following single (1\u2010160\u00a0mg) and multiple (3\u201015\u00a0mg once daily) oral\u2010dose TAK\u2010071 in 112 healthy participants and 53 participants with PD from Phase 1 and Phase 2 studies. A 1\u2010compartment model with a delayed absorption phase adequately described TAK\u2010071 pharmacokinetics. Age, body weight, dose, and formulation were significant covariates. Model simulations indicated that age\u2010adjusted dosing is unnecessary. An exposure\u2010response relationship on cognitive function (attention, executive function, memory, global) was evaluated. Benefits were observed on attention, executive function, and global cognition, and these plateaued between 5 and 7.5\u00a0mg once daily, supporting a dose of 7.5\u00a0mg for future clinical studies, as 7.5\u00a0mg was well tolerated. As patients with PD can have an increased risk of falls, the relationship between cognitive function and risk of falls, as assessed by stride time variability, was explored. Cognition response for the attention domain score showed consistent and sustained improvement in stride time variability compared with when no response was observed, supporting further investigation of TAK\u2010071 in PD for the risk of falls.\n                  <\/jats:p>","DOI":"10.1002\/cpdd.1579","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T13:54:10Z","timestamp":1753451650000},"page":"856-868","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic and Exposure\u2010Response Analysis of the Cognitive Effects of TAK\u2010071 in Participants With Parkinson Disease and Cognitive Impairment"],"prefix":"10.1002","volume":"14","author":[{"given":"Hongxia","family":"Jia","sequence":"first","affiliation":[{"name":"Quantitative Clinical Pharmacology Takeda Development Center Americas, Inc. Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Facius","sequence":"additional","affiliation":[{"name":"thinkQ<sup>2<\/sup> AG  Baar Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Jennings","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology Takeda Development Center Americas, Inc. Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaming","family":"Hang","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology Takeda Development Center Americas, Inc. Cambridge MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaya","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Quantitative Clinical Pharmacology Takeda Development Center Americas, Inc. 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