{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:46:43Z","timestamp":1791413203560,"version":"4.3.3"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,4,8]],"date-time":"2016-04-08T00:00:00Z","timestamp":1460073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Anaemia of chronic disease is characterized by impaired erythropoiesis due to functional iron deficiency, often caused by excessive hepcidin. Lexaptepid pegol, a pegylated structured <jats:sc>l<\/jats:sc>\u2010oligoribonucleotide, binds and inactivates hepcidin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We conducted a placebo\u2010controlled study on the safety, pharmacokinetics and pharmacodynamics of lexaptepid after single and repeated i.v. and s.c. administration to 64 healthy subjects at doses from 0.3 to 4.8\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>After treatment with lexaptepid, serum iron concentration and transferrin increased dose\u2010dependently. Iron increased from approximately 20\u00a0\u03bcmol\u00b7L<jats:sup>\u22121<\/jats:sup> at baseline by 67% at 8\u00a0h after i.v. infusion of 1.2\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup> lexaptepid. The pharmacokinetics showed dose\u2010proportional increases in peak plasma concentrations and moderately over\u2010proportional increases in systemic exposure. Lexaptepid had no effect on hepcidin production or anti\u2010drug antibodies. Treatment with lexaptepid was generally safe and well tolerated, with mild and transient transaminase increases at doses \u22652.4\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup> and with local injection site reactions after s.c. but not after i.v. administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Lexaptepid pegol inhibited hepcidin and dose\u2010dependently raised serum iron and transferrin saturation. The compound is being further developed to treat anaemia of chronic disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13433","type":"journal-article","created":{"date-parts":[[2016,1,16]],"date-time":"2016-01-16T18:13:18Z","timestamp":1452967998000},"page":"1580-1588","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Safety, pharmacokinetics and pharmacodynamics of the anti\u2010hepcidin Spiegelmer lexaptepid pegol in healthy subjects"],"prefix":"10.1111","volume":"173","author":[{"given":"M","family":"Boyce","sequence":"first","affiliation":[{"name":"Hammersmith Medicines Research  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Warrington","sequence":"additional","affiliation":[{"name":"Hammersmith Medicines Research  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Cortezi","sequence":"additional","affiliation":[{"name":"Hammersmith Medicines Research  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Z\u00f6llner","sequence":"additional","affiliation":[{"name":"NOXXON Pharma AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Vaul\u00e9on","sequence":"additional","affiliation":[{"name":"NOXXON Pharma AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D W","family":"Swinkels","sequence":"additional","affiliation":[{"name":"Hepcidinanalysis.com Radboud University Nijmegen Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Summo","sequence":"additional","affiliation":[{"name":"NOXXON Pharma AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Schwoebel","sequence":"additional","affiliation":[{"name":"NOXXON Pharma AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Riecke","sequence":"additional","affiliation":[{"name":"NOXXON Pharma AG  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,4,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13355"},{"key":"e_1_2_11_3_1","unstructured":"EMA(2007).Guideline on strategies to identify and mitigate risks for first\u2010in\u2010human clinical trials with investigational medicinal products. 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