{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:38:47Z","timestamp":1791329927323,"version":"4.3.1"},"reference-count":16,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T00:00:00Z","timestamp":1534982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002973","name":"Daiichi-Sankyo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002973","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002336","name":"Daiichi Sankyo Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Three phase 1 pharmacokinetic (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>)\/pharmacodynamics (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>) studies were conducted in healthy men and women to further characterize the safety, tolerability, and<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>of mirogabalin administration with or without food and to guide the dose selection and regimen for phase 2 and 3 clinical development. The 3 studies included 2 randomized, double\u2010blind, placebo\u2010controlled, single\u2010 and multiple\u2010ascending\u2010dose studies, and 1 open\u2010label, crossover study to evaluate the<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>of mirogabalin administered under fasting and fed (high\u2010fat meal) conditions. Forty\u2010eight and 47 healthy volunteers completed the single\u2010 and multiple\u2010dose studies, respectively. Thirty subjects were enrolled and completed the food effect study. Mirogabalin was well tolerated in the fed and fasted states. The most frequent treatment\u2010emergent adverse events (<jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s)\u2014dizziness and somnolence\u2014were expected based on mirogabalin's mechanism of action. Subjects receiving the highest mirogabalin doses (50 and 75\u00a0mg single dose) showed greater dizziness and sedation and higher rates of<jats:styled-content style=\"fixed-case\">TEAE<\/jats:styled-content>s than subjects receiving 3\u201030\u00a0mg. After oral administration, mirogabalin was rapidly absorbed (time to maximum concentration, \u223c1\u00a0hour) and eliminated through urine unchanged (61%\u201072% urinary excretion). Exposure increased in a dose\u2010proportional manner after single or multiple mirogabalin doses. No significant accumulation occurred with multiple doses over 14\u00a0days. After single doses of mirogabalin (15\u00a0mg), the bioavailability was considered equivalent in the fed and fasted states, indicating that mirogabalin can be taken without food restrictions. Based on these data, mirogabalin 15\u00a0mg twice daily was selected as the highest target dose for further clinical development.<\/jats:p>","DOI":"10.1002\/prp2.418","type":"journal-article","created":{"date-parts":[[2018,8,23]],"date-time":"2018-08-23T08:04:53Z","timestamp":1535011493000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Tolerability, pharmacokinetics, and pharmacodynamics of mirogabalin in healthy subjects: Results from phase 1 studies"],"prefix":"10.1002","volume":"6","author":[{"given":"Karen","family":"Brown","sequence":"first","affiliation":[{"name":"Daiichi Sankyo Pharma Development Basking Ridge New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Mendell","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Pharma Development Basking Ridge New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoichi","family":"Ohwada","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Co., Ltd. Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching","family":"Hsu","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Pharma Development Basking Ridge New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"He","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Pharma Development Basking Ridge New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vance","family":"Warren","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Pharma Development Basking Ridge New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Dishy","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Pharma Development Basking Ridge New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-5669","authenticated-orcid":false,"given":"Hamim","family":"Zahir","sequence":"additional","affiliation":[{"name":"Daiichi Sankyo Pharma Development Basking Ridge New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"P7","DOI":"10.1212\/WNL.82.10_supplement.P7.301","article-title":"Pharmacological, pharmacokinetics, and safety profiles of DS\u20105565, a novel \u03b12\u03b4 ligand","volume":"82","author":"Yokoyama T","year":"2014","journal-title":"Neurology"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13349"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0356-09.2009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-1964"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409066103"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.10.5768"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1044"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10111704"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1983.tb02282.x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-0172-7"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1037\/1040-3590.17.2.237"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12955-015-0207-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22681"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009352087"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/DHPS.S95535"},{"key":"e_1_2_9_17_1","unstructured":"US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research.Guidance for industry food\u2010effect bioavailability and fed bioequivalence studies. US Department of Health and Human Services.2002.https:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm070241.pdf. (Accessed May 25 2018)"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fprp2.418","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.418","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T10:37:57Z","timestamp":1720521477000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,23]]},"references-count":16,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1002\/prp2.418"],"URL":"https:\/\/doi.org\/10.1002\/prp2.418","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,23]]},"assertion":[{"value":"2018-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00418"}}