{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T14:35:12Z","timestamp":1778250912242,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:00:00Z","timestamp":1758672000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Arafarma Group, S.A., Marchamalo (Guadalajara), Spain"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>While capsaicin topical formulations are established treatments, conventional creams using this substance have limited application due to handling-related adverse events. This study aimed to demonstrate that the efficacy of a novel 0.75 mg\/g capsaicin roll-on solution is non-inferior to the approved 0.75 mg\/g cream in patients with painful diabetic neuropathy (PDN). In total, 160 patients were randomized to receive either the roll-on or the cream, applied four times daily for 8 weeks, followed by a 4-week washout period and crossover to the alternate treatment. The primary endpoint was pain intensity (numerical rating scale), with secondary endpoints including quality of life (EQ-5D) and safety. Both groups showed significant reductions in pain, with no statistically significant differences in absolute (p = 0.115) or relative (p = 0.157) pain reduction. Non-inferiority was confirmed with a 95% CI for the difference in mean pain reduction [\u22120.86\u20130.07], remaining within the pre-specified margin (1.0 unit). Quality of life improved in both groups, with no significant differences (p = 0.266). The incidence of adverse events was low and predominantly mild, with no significant differences between groups (p = 0.424) and a favorable trend for the roll-on formulation. The roll-on capsaicin formulation demonstrated non-inferiority in efficacy and safety compared with the conventional cream formulation.<\/jats:p>","DOI":"10.3390\/life15101507","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T07:46:49Z","timestamp":1758786409000},"page":"1507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Non-Inferiority Study of Two Capsaicin Formulations for Painful Diabetic Neuropathy"],"prefix":"10.3390","volume":"15","author":[{"given":"Tamara Rodr\u00edguez","family":"Araya","sequence":"first","affiliation":[{"name":"Primary Chronic Pain and Fibromyalgia Unit, Hospital Cl\u00ednic in Barcelona, 170 Villarroel Street, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6519-8885","authenticated-orcid":false,"given":"Francisco","family":"Abad-Santos","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Hospital Universitario de La Princesa, Faculty of Medicine, Instituto de Investigaci\u00f3n Sanitaria La Princesa (IP), Universidad Auton\u00f3ma de Madrid (UAM), 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Miguel Sempere","family":"Ortells","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of Alicante, San Vicente del Raspeig Road, San Vicente del Raspeig, 03690 Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Nieto","family":"Navarro","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Miguel Hern\u00e1ndez University of Elche, University Avenue, 03202 Elche, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Gonz\u00e1lez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University General Hospital of Alicante, 03010 Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9808-2291","authenticated-orcid":false,"given":"Javier","family":"Abarca-Olivas","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University General Hospital of Alicante, 03010 Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena Ba\u00f1o","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University General Hospital of Alicante, 03010 Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3100-7833","authenticated-orcid":false,"given":"Carlos","family":"Iglesias-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Clinical Partner & Innovation, S.L. 49 Princesa Street, 28008 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Fernando Villalba","family":"Garc\u00eda","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, University of Alicante, San Vicente del Raspeig Road, San Vicente del Raspeig, 03690 Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.pain.2011.06.017","article-title":"A new definition of neuropathic pain","volume":"152","author":"Jensen","year":"2011","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17002","DOI":"10.1038\/nrdp.2017.2","article-title":"Neuropathic pain","volume":"3","author":"Colloca","year":"2017","journal-title":"Nat. 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