{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T15:34:19Z","timestamp":1789918459607,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The TRPV1 receptor is a key molecule in pain generation. Previous development of oral TRPV1\u2010antagonists was halted due to systemic heat insensitivity and body temperature alterations. The present Phase 1b study investigated the efficacy, safety and plasma exposure of a topically administered TRPV1\u2010antagonist (ACD440 Gel) in healthy subjects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study comprised two parts.<\/jats:p><jats:p>In part 1, 24\u2009healthy subjects were included in this randomized double\u2010blind, placebo\u2010controlled, crossover trial. ACD440 Gel or Placebo was applied once daily and wiped off after 1\u2009h, for 5 consecutive days. Assessments were done in normal skin, skin optimized for penetration (by stripping and occlusive gel application) and UVB\u2010irradiated skin. Pain induced by thermo\u2010nociceptive CO<jats:sub>2<\/jats:sub> laser impulses generated laser\u2010evoked potentials (LEPs), with readouts of peak\u2010to\u2010peak (PtP) amplitude in vertex\u2010EEG and pain assessments by VAS (0\u2013100). Endpoints include effects at 1\u2009hour post\u2010dose, AUC(Days 1\u20135) and AUC<jats:sub>(0\u201324, Day 4)<\/jats:sub>. In UVB\u2010irradiated skin, also pain on pinprick and skin redness were assessed.<\/jats:p><jats:p>Part 2 explored the plasma pharmacokinetics of ACD440.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ACD440 Gel reduced LEP PtP amplitude and VAS pain, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, in all skin conditions, versus placebo. In UVB\u2010irradiated skin, pinprick pain was also reduced, <jats:italic>p<\/jats:italic>\u2009=\u20090.047. Effects were significant after 1\u2009h, maintaining for at least 9\u2009h. There were no adverse events or drug\u2010induced erythema. Plasma exposures of ACD440 were too low to establish an elimination half\u2010life of ACD400.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Topical ACD440 Gel demonstrated a significant analgesic effect on LEP, VAS score and pinprick pain, with low systemic exposures, supporting further clinical development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>This study demonstrates that the topical administration of a TRPV1\u2010antagonist, ACD440 Gel, has potential as a new treatment for painful conditions affecting the skin, such as chronic peripheral neuropathic pain, without any local or systemic side effects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.2299","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T13:45:06Z","timestamp":1718199906000},"page":"1656-1673","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Topically applied novel <scp>TRPV1<\/scp> receptor antagonist, <scp>ACD440<\/scp> Gel, reduces evoked pain in healthy volunteers, a randomized, double\u2010blind, placebo\u2010controlled, crossover study"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-3302","authenticated-orcid":false,"given":"M.","family":"Segerdahl","sequence":"first","affiliation":[{"name":"AlzeCure Pharma AB  Huddinge Sweden"},{"name":"Department of Neurobiology, Care Sciences and Society Karolinska Institute  Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rother","sequence":"additional","affiliation":[{"name":"AlzeCure Pharma AB  Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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