{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:43:41Z","timestamp":1791413021748,"version":"4.3.3"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Treatment of prurigo nodularis (PN) is challenging and new treatment options are needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the efficacy and safety of two oral doses of the kappa opioid agonist and mu opioid antagonist nalbuphine extended release (NAL\u2010ER) tablets in a phase 2, multicentre, randomized, double\u2010blind, placebo\u2010controlled trial with an open\u2010label, 50\u2010week extension phase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Subjects with moderate\u2010to\u2010severe PN were randomized to NAL\u2010ER 81\u2009mg (NAL\u2010ER81) or 162\u2009mg (NAL\u2010ER162) tablets twice\u2010daily or placebo for 8\u2009weeks of stable dosing following a 2\u2010week titration period. Subjects completing Week 10 with a Worst Itch Numerical Rating Scale (WI\u2010NRS) score \u22655 at the time of rollover (or during the observation period) were eligible for open\u2010label treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 63 randomized subjects, 62 were treated and comprised the modified intent\u2010to\u2010treat population (MITT), 50 completed 10\u2009weeks of treatment. In the MITT analysis, 8 subjects (44.4%) treated with NAL\u2010ER162 (<jats:italic>P<\/jats:italic>\u2009=\u20090.32) and 6 (27.3%) treated with NAL\u2010ER81 (<jats:italic>P<\/jats:italic>\u2009=\u20090.78) achieved \u226530% reduction from baseline in 7\u2010day WI\u2010NRS at Week 10 (primary efficacy endpoint) vs. 8 (36.4%) in the placebo group. Itch reduction was significant among 8\/12 (66.7%) subjects completing Week 10 treated with NAL\u2010ER162 vs. placebo (8\/20, 40.0%; <jats:italic>P<\/jats:italic>\u2009=\u20090.03). Additionally, 6 subjects (33.3%) treated with NAL\u2010ER162 and 3 (13.6%) treated with NAL\u2010ER81 achieved \u226550% reduction from baseline in 7\u2010day WI\u2010NRS at Week 10 (coprimary endpoint). Extended open\u2010label treatment was associated with further improvements in itch reduction and favourable changes in PN lesion activity as assessed by Prurigo Activity Score. Adverse events occurred predominantly during dose titration and were of mild\u2010to\u2010moderate severity. The safety profile did not change with extended open\u2010label treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In adult subjects with PN, oral treatment with NAL\u2010ER 162\u2009mg twice daily provided measurable anti\u2010pruritic efficacy in subjects completing \u226510\u2009weeks of treatment and was well tolerated (ClinicalTrials.gov: NCT02174419).<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.17816","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T15:49:17Z","timestamp":1636991357000},"page":"453-461","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Efficacy and safety of oral nalbuphine extended release in prurigo nodularis: results of a phase 2 randomized controlled trial with an open\u2010label extension phase"],"prefix":"10.1111","volume":"36","author":[{"given":"E.","family":"Weisshaar","sequence":"first","affiliation":[{"name":"Occupational Dermatology Department of Dermatology Heidelberg University Hospital Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0766-6342","authenticated-orcid":false,"given":"J.C.","family":"Szepietowski","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.D.","family":"Bernhard","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Massachusetts Medical School Worcester MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Hait","sequence":"additional","affiliation":[{"name":"Trevi Therapeutics, Inc. New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.J.","family":"Legat","sequence":"additional","affiliation":[{"name":"Department of Dermatology Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Nattkemper","sequence":"additional","affiliation":[{"name":"Department of Dermatology Miller School of Medicine and Miami Itch Center Miami FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Reich","sequence":"additional","affiliation":[{"name":"Department of Dermatology Institute of Medical Sciences Medical College of Rzesz\u00f3w University Rzesz\u00f3w Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2342-022X","authenticated-orcid":false,"given":"B.","family":"Sadoghi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.R.","family":"Sciascia","sequence":"additional","affiliation":[{"name":"Trevi Therapeutics, Inc. 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