{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T12:46:20Z","timestamp":1792586780016,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100013348","name":"Innosuisse - Schweizerische Agentur f\u00fcr Innovationsf\u00f6rderung","doi-asserted-by":"publisher","award":["37848.1 IP\u2010LS"],"award-info":[{"award-number":["37848.1 IP\u2010LS"]}],"id":[{"id":"10.13039\/501100013348","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      N\u2010desmethyl clobazam (NDMC), an \u03b12\u2010preferring\u2010\u03b11\u2010sparing\u2010GABA\n                      <jats:sub>A<\/jats:sub>\n                      modulator, was promising in preclinical models and Phase I studies, demonstrating antihyperalgesic properties without associated sedation. This Phase IIa trial aimed at exploring the effect of NDMC in peripheral neuropathic pain (NP) patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Randomised, ascending doses, double\u2010blind, placebo\u2010controlled study, evaluating 40, 60, 120\u2009mg of NDMC. Primary outcome was the change in weekly average daily pain (WADP) on a Numerical Rating Scale (NRS) from baseline (V1) to the end of the study (V7). Secondary outcomes included sedation (subjective NRS), quality of life (SF36), global and patient impression of change (CGI, PCGI). PK and safety data were collected. The study was prematurely terminated due to recruitment challenges related to the COVID\u201019 pandemic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Thirty\u2010three out of the planned 76 patients were enrolled. The mean reduction in WADP from V1 to V7 was \u22121.53 points for placebo and \u22121.99 across all NDMC doses (delta\u2009=\u20090.46,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.47). When analysed according to NDMC plasma concentrations, the mean WADP reduction was 1.53 (SD 1.58) for placebo 1.78 (SD 1.79) for NDMC &lt;\u20091000\u2009ng\/mL, and 2.40 (SD 1.46) for NDMC \u2265\u20091000\u2009ng\/mL. The prevalence of 30% pain reduction was 38.5% (placebo) and 83.3% (NDMC \u2265\u20091000\u2009ng\/mL). Logistic regression analysis indicated that NDMC \u2265\u20091000\u2009ng\/nL was predictive of a 30% pain reduction (odds ratio\u2009=\u200912.5,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04). NDMC was well tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Despite being underpowered, this study revealed a consistent exposure\u2013response relationship along with a favourable safety profile for NDMC in patients with NP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrial.gov\">ClinicalTrial.gov<\/jats:ext-link>\n                      (NCT03375034); kofam.ch (SNCTP000003517).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>This work presenting the Phase II data of the new antihyperalgesic compound, N\u2010Desmethyl\u2010Clobazam (NDMC) in peripheral neuropathic pain patients support further investigation into the role in modulating GABAergic pathways as a potential therapeutic target for neuropathic pain. This objective is particularly relevant given the limited efficacy of standard pharmacological treatments for neuropathic pain, which often requires a multimodal approach targeting the multiple pathways involved in pain pathophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejp.70413","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:01:41Z","timestamp":1792159301000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The \u03b12\u2010Subunit Preferring\n                    <scp>GABA<\/scp>\n                    Positive Allosteric Modulator, N\u2010Desmethyl\u2010Clobazam in Peripheral Neuropathic Pain Patients: Results of a Phase\n                    <scp>IIa<\/scp>\n                    Randomised Placebo\u2010Controlled Ascending Dose 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