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Each subject was randomized to one of nine treatment schedules: all subjects received placebo and two of three doses of TAK-063 followed by ketamine. The primary endpoint was ketamine-induced brain activity in select regions of the brain during resting state. Secondary endpoints included pharmacokinetic parameters of TAK-063, proportion of subjects with treatment-emergent adverse events (AEs), and percentage of subjects meeting criteria for abnormal safety laboratory tests and vital sign measurements.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>The study comprised 27 subjects. Prior to ketamine infusion, TAK-063 exerted region-specific effects on resting state functional MRI (fMRI) BOLD signal. After ketamine administration, TAK-063 reduced the Cohen\u2019s effect size for resting-state fMRI BOLD signal in key brain regions examined, and exerted similar effects on BOLD signal during the working memory task across all doses. TAK-063 was safe and well tolerated.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our results are consistent with non-clinical studies of ketamine and TAK-063 and clinical studies of ketamine and risperidone. It is unknown whether these data are predictive of potential antipsychotic efficacy, and further analyses are required.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00213-019-05366-1","type":"journal-article","created":{"date-parts":[[2019,11,26]],"date-time":"2019-11-26T06:02:52Z","timestamp":1574748172000},"page":"317-328","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["A randomized, placebo-controlled, phase 1 study to evaluate the effects of TAK-063 on ketamine-induced changes in fMRI BOLD signal in healthy subjects"],"prefix":"10.1007","volume":"237","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7242-4190","authenticated-orcid":false,"given":"Deborah A.","family":"Yurgelun-Todd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry F.","family":"Renshaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Goldsmith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolga","family":"Uz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Macek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,26]]},"reference":[{"issue":"Suppl 2","key":"5366_CR1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1055\/s-2007-979354","volume":"31","author":"WM Abi-Saab","year":"1998","unstructured":"Abi-Saab WM, D'Souza DC, Moghaddam B, Krystal JH (1998) The NMDA antagonist model for schizophrenia: promise and pitfalls. 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