{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T15:11:02Z","timestamp":1760368262680},"reference-count":8,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":3719,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2003,1]]},"abstract":"<jats:p>ReN1869 (NNC 05\u20131869) is a novel, selective H<jats:sub><jats:italic>1<\/jats:italic><\/jats:sub> receptor antagonist that has been developed for analgesic purposes. In a first human dose administration study, the safety and pharmacokinetics of seven single oral doses in the range of 3.5 to 95 mg ReN1869 were studied. The study was a randomized, double\u2010blind, placebo\u2010controlled, dose\u2010escalating study in 56 healthy subjects. No serious or severe adverse events were reported. After active doses, an average of 0.6 adverse events (AEs) was reported per subject in comparison to 0.5 AEs per subject after placebo, and the frequency of subjects reporting AEs was not related to dose level. The most frequently reported adverse events were dizziness, fatigue, and somnolence, and their occurrence was not proportional to dose. Vital signs, ECG recordings, and clinical laboratory results showed no changes of clinical relevance. During telemetric monitoring at all dose levels until 4 hours after dosing, no clinically relevant abnormalities were observed. A maximally tolerated dose was not identified. ReN1869 was rapidly absorbed after dosing. The overall mean value of t<jats:sub><jats:italic>1\/2<\/jats:italic><\/jats:sub> and oral clearance was 4.7 hours and 11.7 L\/h, respectively. The parameters C<jats:sub>max<\/jats:sub> and AUC increased proportionally with dose level, whereas all other pharmacokinetic parameters were independent of the dose. In conclusion, single\u2010dose administration of ReN1869 in doses up to 95 mg exhibited very few adverse events and no clinically relevant effects on any of the observed safety parameters. The pharmacokinetics points to simple first\u2010order pharmacokinetics for ReN1869. All together, it makes ReN1869 a potential new drug candidate for the treatment of chronic pain and inflammatory conditions of neurogenic origin.<\/jats:p>","DOI":"10.1177\/0091270002239708","type":"journal-article","created":{"date-parts":[[2003,4,28]],"date-time":"2003-04-28T10:36:11Z","timestamp":1051526171000},"page":"66-73","source":"Crossref","is-referenced-by-count":6,"title":["Safety and Pharmacokinetics of ReN1869: A First Human Dose Study in Healthy Subjects after Single\u2010Dose Administration"],"prefix":"10.1002","volume":"43","author":[{"given":"Birte K.","family":"Skrumsager","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steen H.","family":"Ingwersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireille","family":"Gerrits","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,3,8]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2710.2001.00330.x"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01556-4"},{"key":"e_1_2_5_4_2","unstructured":"DragstedN: Internal reports Department of Safety Pharmacology Novo Nordisk A\/S DK\u20102880 Bagsvaerd Denmark."},{"key":"e_1_2_5_5_2","unstructured":"World Medical Association:Declaration of Helsinki: recommendations guiding physicians in biomedical research involving human subjects. Amended by the 41st World Medical Assembly Hong Kong September 1989."},{"key":"e_1_2_5_6_2","unstructured":"Good Clinical Practice for Trials on Medicinal Products in the European Community Document III\/3976\/888EN Commission of the European Communities Brussels July 1990."},{"key":"e_1_2_5_7_2","volume-title":"TopFit 2.0 Pharmacokinetic and Pharmacodynamic Data Analysis System","author":"Heinzel G","year":"1993"},{"issue":"3","key":"e_1_2_5_8_2","first-page":"S205","article-title":"Effects of ReN1869 on capsaicin and histamine induced neurogenic inflammation in healthy subjects","volume":"50","author":"Thomsen MS","year":"2001","journal-title":"Inflammation Research"},{"issue":"1","key":"e_1_2_5_9_2","first-page":"S57","article-title":"Study to evaluate the effect of ReN 1869 on the development of capsaicin\u2010induced hyperalgesia in human skin: a study using laser\u2010induced somatosensory evoked potentials (LSEPs), Deutscher Schmerzkongress, Berlin, Oct. 2001","volume":"15","author":"Schaffler K","year":"2001","journal-title":"Der Schmerz"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1177%2F0091270002239708","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1177\/0091270002239708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T20:21:12Z","timestamp":1697228472000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1177\/0091270002239708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":8,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["10.1177\/0091270002239708"],"URL":"https:\/\/doi.org\/10.1177\/0091270002239708","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1]]}}}