{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T11:06:25Z","timestamp":1769252785604,"version":"3.49.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T00:00:00Z","timestamp":1690329600000},"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. Endocrinol."],"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>To verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as reference.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a randomized, open-label, single-dose, crossover hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the reference (R) group (Novolin R, 0.1 IU\/Kg, i.h.) with a washout period of 14 days. All subjects were administered on the same day of the clamp study. Glucose Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov identifier NCT04975022.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After administration, the ratios of mean serum C-peptide concentration to baseline concentration in both T and R groups were lower than 50%, which confirmed the stability of the clamp platform. T group (N11005) showed a more rapid onset of action (tGIR<jats:sub>10%max<\/jats:sub>\u224811 min) and a comparable duration of action to the R group, which was basically in line with the characteristics of prandial insulins. No adverse events (AEs) occurred throughout the study, which demonstrated that N11005 and Novolin R are safe and well-tolerated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The PD profiles of the single-dose N11005 in the human body are similar to those of prandial insulins, with an excellent safety profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:uri>Clinicaltrials.gov<\/jats:uri>, identifier NCT04975022.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1172327","type":"journal-article","created":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T14:20:36Z","timestamp":1690381236000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacokinetics, pharmacodynamics, and safety of prandial oral insulin (N11005) in healthy subjects"],"prefix":"10.3389","volume":"14","author":[{"given":"Qi","family":"Pan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulei","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinghong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhui","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yijie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijie","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Hua","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Tsai","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lixin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1001\/archinte.161.3.397","article-title":"DECODE study group, the European diabetes epidemiology group glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria","volume":"161","year":"2001","journal-title":"Arch Intern Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-004-1334-6","article-title":"Hyperglycaemia and mortality from all causes and from cardiovascular disease in five populations of Asian origin","volume":"47","author":"Nakagami","year":"2004","journal-title":"Diabetologia."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.24.8.1397","article-title":"Postchallenge hyperglycemia and mortality in a national sample of U.S. adults","volume":"24","author":"Saydah","year":"2001","journal-title":"Diabetes Care"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2008.01.012","article-title":"Guideline for management of postmeal glucose in diabetes","volume":"18","author":"Ceriello","year":"2008","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"B5","article-title":"Chinese Expert consensus on management of postprandial hyperglycemia for type 2 diabetes mellitus","volume":"24","author":"Mu","year":"2016","journal-title":"Chin J Diabetes"},{"key":"B6","volume-title":"Technical guidelines for research, development and evaluation of biosimilars (Trial), CDE","year":"2015"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.05.042","article-title":"Biodistribution, pharmacodynamics and pharmacokinetics of insulin analogues in a rat model: oral delivery using pH-responsive nanoparticles vs. subcutaneous injection","volume":"31","author":"Sonaje","year":"2010","journal-title":"Biomaterials."},{"key":"B8","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1111\/jphp.12852","article-title":"Oral insulin delivery: existing barriers and current counter-strategies","volume":"70","author":"Gedawy","year":"2018","journal-title":"J Pharm Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2016.6","article-title":"Pancreatic regulation of glucose homeostasis","volume":"48","author":"R\u00f6der","year":"2016","journal-title":"Exp Mol Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118678","article-title":"Effects of a change in the pattern of insulin delivery on carbohydrate tolerance in diabetic and nondiabetic humans in the presence of differing degrees of insulin resistance","volume":"97","author":"Basu","year":"1996","journal-title":"J Clin Invest."},{"key":"B11","doi-asserted-by":"publisher","first-page":"7","DOI":"10.2165\/00003088-200847010-00002","article-title":"Clinical pharmacokinetics and pharmacodynamics of insulin glulisine","volume":"47","author":"Becker","year":"2008","journal-title":"Clin Phatmacokinet."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1095-8","article-title":"A novel insulin formulation with a more rapid onset of action","volume":"51","author":"Steiner","year":"2008","journal-title":"Diabetologia."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2004.12.001","article-title":"Comparison of pharmacokinetic and pharmacodynamic properties of single-dose oral insulin spray and subcutaneous insulin injection in healthy subjects using the euglycemic clamp technique","volume":"26","author":"Cernea","year":"2004","journal-title":"Clin Ther"},{"key":"B14","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.diabres.2016.09.001","article-title":"A comparison of the pharmacodynamic profiles of jet-injected regular human insulin versus conventionally administered insulin aspart in healthy volunteers","volume":"121","author":"Engwerda","year":"2016","journal-title":"Diabetes Res Clin Pract"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/BF00404644","article-title":"Action profiles of fast onset insulin analogues","volume":"33","author":"Heinemann","year":"1990","journal-title":"Diabetologia."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.21.11.1910","article-title":"Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart","volume":"21","author":"Heinemann","year":"1998","journal-title":"Diabetes Care"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12468","article-title":"Faster-acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart","volume":"17","author":"Heise","year":"2015","journal-title":"Diabetes Obes Metab"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1172327\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,26]],"date-time":"2023-07-26T14:20:39Z","timestamp":1690381239000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1172327\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,26]]},"references-count":17,"alternative-id":["10.3389\/fendo.2023.1172327"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1172327","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,26]]},"article-number":"1172327"}}