{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:54:16Z","timestamp":1781585656170,"version":"3.54.5"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    JKN2306 is a novel, highly selective Nav1.8 inhibitor under development for the treatment of acute pain. This first\u2010in\u2010human study aimed to evaluate its safety, tolerability, pharmacokinetics, and food effect (FE). This was a single center, randomized, double\u2010blind, placebo controlled, single ascending dose (SAD) and FEstudy in healthy Chinese subjects. In the SAD part, 44 subjects were randomized to receive a single oral dose of JKN2306 (10, 30, 100, 200, or 400\u2009mg) or placebo. The FE part was a sequential, two\u2010period crossover study in 14 subjects from the 200\u2009mg SAD cohort, who received a single 200\u2009mg dose under fasting and fed conditions. Forty\u2010four subjects were enrolled and completed the study. JKN2306 was safe and well\u2010tolerated across all doses. Treatment\u2010emergent adverse events were mostly Grade 1, with no serious adverse events or dose limiting toxicities. No clinically significant effects on QTc interval were observed. JKN2306 was rapidly absorbed, with\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    of 1.50\u20132.50\u2009h. The\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    ranged from 13.93 to 29.82\u2009h. Exposure (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    and AUC) increased approximately linearly with dose over the 10\u2013400\u2009mg range. Food intake delayed the median\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    by 1\u2009h and reduced\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    by about 17%, but had no significant effect on AUC. JKN2306 exhibits a favorable safety and tolerability profile and predictable linear PK in healthy subjects. Food has a modest effect on the rate but not the extent of absorption. These findings support the further clinical development of JKN2306 for the treatment of acute pain.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/chinadrugtrials.org.cn\">chinadrugtrials.org.cn<\/jats:ext-link>\n                    identifier: CTR20250247 and\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">clinicaltrials.gov<\/jats:ext-link>\n                    identifier: NCT07412938\n                  <\/jats:p>","DOI":"10.1002\/prp2.70277","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T07:16:49Z","timestamp":1781507809000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Highly Selective NaV1.8 Inhibitor\n                    <scp>JKN2306<\/scp>\n                    in Healthy Chinese Subjects"],"prefix":"10.1002","volume":"14","author":[{"given":"Ying","family":"Yang","sequence":"first","affiliation":[{"name":"Joincare Pharmaceutical Group Industry Co., Ltd.  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Han","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Cui","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Mi","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangli","family":"Jin","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Joincare Pharmaceutical Group Industry Co., Ltd.  Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Li","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoyun","family":"Gou","sequence":"additional","affiliation":[{"name":"Drug Clinical Trial Research Center China\u2010Japan Friendship Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5981-9447","authenticated-orcid":false,"given":"Chong","family":"Su","sequence":"additional","affiliation":[{"name":"Joincare Pharmaceutical Group Industry Co., Ltd.  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