{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:01:07Z","timestamp":1791932467580,"version":"4.3.4"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the analgesic potential, safety, tolerability, and pharmacokinetics of VX-150, a pro-drug of a highly selective NaV1.8 inhibitor, in healthy subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>This was a randomized, double-blind, placebo-controlled, crossover study in healthy subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Subjects<\/jats:title>\n                    <jats:p>Twenty healthy male subjects with an age of 18\u201355 years, inclusive, were enrolled. Eligibility was based on general fitness, absence of current or previous medical conditions that could compromise subject safety, and a training assessment of pain tolerance across pain tests to exclude highly tolerant individuals whose tolerance could compromise the ability to detect analgesic responses. All dosed subjects completed the study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Subjects were randomized 1:1 to one of two sequences receiving a single VX-150 dose and subsequently placebo, or vice versa, with at least 7\u2009days between dosing. A battery of pain tests (pressure, electrical stair, [capsaicin-induced] heat, and cold pressor) was administered before dosing and repetitively up to 10\u2009h after dosing, with blood sampling up to 24\u2009h after dosing. Safety was monitored throughout the study. Data were analyzed with a repeated-measures mixed-effects model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>VX-150 induced analgesia in a variety of evoked pain tests, without affecting subject safety. Significant effects were reported for the cold pressor and heat pain thresholds. Maximum median concentration for the active moiety was 4.30 \u00b5g\/mL at 4\u2009h after dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Results of this proof-of-mechanism study are supportive of the potential of VX-150, a highly selective NaV1.8 channel inhibitor, to treat various pain indications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/pm\/pnab032","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T13:50:10Z","timestamp":1611841810000},"page":"1814-1826","source":"Crossref","is-referenced-by-count":63,"title":["A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Pharmacodynamic Effects of VX-150, a Highly Selective NaV1.8 Inhibitor, in Healthy Male Adults"],"prefix":"10.1093","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7298-8650","authenticated-orcid":false,"given":"Hemme J","family":"Hijma","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter S","family":"Siebenga","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke L","family":"de Kam","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert Jan","family":"Groeneveld","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research, Leiden, The Netherlands"},{"name":"Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"2021080708521512300_pnab032-B1","volume-title":"Australian Medicines Handbook","author":"Rossi","year":"2006"},{"issue":"3","key":"2021080708521512300_pnab032-B2","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1054\/jpai.2000.9822","article-title":"Will ion-channel blockers be useful for management of nonneuropathic pain?","volume":"1","author":"Petersen","year":"2000","journal-title":"J Pain"},{"key":"2021080708521512300_pnab032-B3","article-title":"Discovery and Development of Major Drugs Currently in Use. 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