{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:59:26Z","timestamp":1790657966633,"version":"4.1.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tegomil fumarate is a newly approved treatment for relapsing\u2013remitting multiple sclerosis. Two phase I studies were performed under different fed conditions to evaluate the bioequivalence and tolerability of tegomil fumarate versus dimethyl fumarate in healthy volunteers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>These were single-center, open-label, randomized, crossover (full replicate design), phase I studies. In both studies, healthy individuals aged 18\u201355\u202fyears received a single dose of tegomil fumarate (348.4\u202fmg gastro-resistant hard capsule; \u201ctest\u201d) or an equimolar dose of dimethyl fumarate based on monomethyl fumarate (MMF) release (240.0\u202fmg gastro-resistant hard capsule; \u201creference\u201d). Participants were randomized to one of two treatment sequences (test\u2013reference\u2013test\u2013reference or reference\u2013test\u2013reference\u2013test), with 7\u202fdays between each drug administration. Before each drug administration, participants in Study 1 consumed a low-fat, low-calorie meal (\u201clow-fed\u201d), while those in Study 2 consumed a high-fat, high-calorie meal (\u201cfed\u201d). Pharmacokinetic parameters for MMF (active metabolite in both drugs) and adverse events (AEs) were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 70 participants were enrolled (Study 1,\n                      <jats:italic>N<\/jats:italic>\n                      \u202f=\u202f40; Study 2,\n                      <jats:italic>N<\/jats:italic>\n                      \u202f=\u202f30). In both studies, pharmacokinetic parameters for MMF were similar between drugs. Geometric least-squares mean test\/reference ratios for C\n                      <jats:sub>max<\/jats:sub>\n                      , AUC\n                      <jats:sub>0\u2013t<\/jats:sub>\n                      , and AUC\n                      <jats:sub>0\u2013inf<\/jats:sub>\n                      (and associated 90% confidence intervals for each) all fell within the accepted range of 80.00\u2013125.00%, thereby demonstrating the bioequivalence of tegomil fumarate versus dimethyl fumarate. Both drugs were well tolerated, with no unexpected or serious AEs reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These studies demonstrated the tolerability of tegomil fumarate in healthy volunteers. Pharmacokinetic analyses showed that a single dose of 348.4\u202fmg tegomil fumarate released the same amount of MMF as an equimolar dose of 240\u202fmg dimethyl fumarate under both low-fed (low-calorie, low-fat) and fed (high-calorie, high-fat) dietary conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      Agen\u0163ia Medicamentului \u015fi Dispozitivelor Medicale [AMDM];\n                      <jats:ext-link>https:\/\/amdm.gov.md\/ro<\/jats:ext-link>\n                      , MMF-BEFI-07-TFB\/24 (Rg04-000227) (Study 1; registered September 4, 2024); MMF-BEFI-06-TFB\/22 (Rg04-000165) (Study 2; registered July 10, 2023).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1936043","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:38:28Z","timestamp":1790656708000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioequivalence of tegomil fumarate gastro-resistant capsules versus dimethyl fumarate gastro-resistant capsules under different fed conditions: two randomized, crossover, phase I studies"],"prefix":"10.3389","volume":"17","author":[{"given":"Katja","family":"Zietz","sequence":"first","affiliation":[{"name":"Alfred E. Tiefenbacher (GmbH & Co. KG)","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Rizea","family":"Savu","sequence":"additional","affiliation":[{"name":"3S Pharmacological Consultation & Research GmbH","place":["Wildeshausen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Remis","sequence":"additional","affiliation":[{"name":"3S Pharmacological Consultation & Research GmbH","place":["Wildeshausen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Medical-Sanitary Public Institution \u201cClinical Hospital of the Ministry of Health\u201d","place":["Chisinau, Moldova"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Iordachescu","sequence":"additional","affiliation":[{"name":"Pharma Serv International SRL","place":["Bucharest, Romania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Herb","sequence":"additional","affiliation":[{"name":"Alfred E. Tiefenbacher (GmbH & Co. KG)","place":["Hamburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.clim.2011.02.017","article-title":"Fumaric acid and its esters: an emerging treatment for multiple sclerosis with antioxidative mechanism of action","volume":"142","author":"Gold","year":"2012","journal-title":"Clin Immunol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1016\/j.autrev.2018.07.001","article-title":"Dimethyl fumarate treatment in multiple sclerosis: recent advances in clinical and immunological studies","volume":"17","author":"Montes Diaz","year":"2018","journal-title":"Autoimmun 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Bg-12 for relapsing multiple sclerosis","volume":"367","author":"Gold","year":"2012","journal-title":"N Engl J Med"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1177\/13524585211037909","article-title":"Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing\u2013remitting multiple sclerosis: final ENDORSE study results","volume":"28","author":"Gold","year":"2022","journal-title":"Mult Scler"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1056\/NEJMoa1206328","article-title":"Placebo-controlled phase 3 study of oral Bg-12 or glatiramer in multiple sclerosis","volume":"367","author":"Fox","year":"2012","journal-title":"N Engl J Med"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1177\/1352458516649037","article-title":"Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: interim analysis of Endorse, a randomized extension 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