{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T17:35:28Z","timestamp":1770917728787,"version":"3.50.1"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T00:00:00Z","timestamp":1703203200000},"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. Pharmacol."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold>INS068 is a novel, soluble, and long-acting insulin analog. In this study, we evaluated the pharmacokinetics and relative bioavailability of two formulations of INS068 in healthy Chinese subjects: a reference formulation packaged in vials and administered via syringe (R), and a test formulation packaged and administered via pen injector (T).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold>A randomized, open-label, two-period, two-sequence crossover study was conducted with 24 healthy Chinese subjects. Subjects were randomized and administered subcutaneously in the abdomen at 0.4 U\/kg of test or reference INS068 injection according to an open crossover design. INS068 concentrations in the serum were measured using LC-MS\/MS, and the pharmacokinetic parameters of maximum concentration (C<jats:sub>max<\/jats:sub>) and area under the concentration-time curve (AUC<jats:sub>0\u2013t<\/jats:sub>and AUC<jats:sub>0\u2013\u221e<\/jats:sub>) were used to evaluate relative bioavailability.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold>After a single dose at 0.4 U\/kg, the median T<jats:sub>max<\/jats:sub>of INS068 was 12 h for both formulations, and the mean t<jats:sub>1\/2<\/jats:sub>for T and R was 13.0 h and 12.6 h, respectively. The geometric means of C<jats:sub>max<\/jats:sub>and AUC<jats:sub>0\u2013\u221e<\/jats:sub>were 3.99 nmol\/L and 120 h\u00b7nmol\/L for the T, and 4.05 nmol\/L and 117 h\u00b7nmol\/L for the R, respectively. The geometric mean ratios of C<jats:sub>max<\/jats:sub>, AUC<jats:sub>0\u2013t<\/jats:sub>and AUC<jats:sub>0\u2013\u221e<\/jats:sub>of T over R were 98.7% (90% CI: 92.7%\u2013105.2%), 102.6% (90% CI: 100.0%\u2013105.3%) and 102.8% (90% CI: 100.1%\u2013105.5%).<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold>The overall PK profile of the two formulations of INS068 injection was comparable in healthy subjects, and the pen injector of INS068 had adequate safety and tolerability, supporting it as a new formulation in a phase III study and bridging PK data from early phase clinical trials.<\/jats:p><jats:p><jats:bold>Clinical Trial Registration:<\/jats:bold><jats:ext-link>clinicaltrials.gov<\/jats:ext-link>, identifier: NCT05336071<\/jats:p>","DOI":"10.3389\/fphar.2023.1294810","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T04:24:18Z","timestamp":1703219058000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Pharmacokinetics and bioavailability of a new long-acting insulin analog in healthy Chinese volunteers: an open, randomized, single-dose, two-period and two-sequence cross-over study"],"prefix":"10.3389","volume":"14","author":[{"given":"Ke-Guang","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye-Hui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pan-Pan","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-Hu","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin-Lin","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-Yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu-Rong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Yi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-Mei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S67","DOI":"10.2337\/dc13-S067","article-title":"Diagnosis and classification of diabetes mellitus","volume":"36","year":"2013","journal-title":"Diabetes care"},{"key":"B2","volume-title":"Guideline on the investigation of bioequivalence","year":"2010"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1007\/s00125-022-05787-2","article-title":"Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American diabetes association (ADA) and the European association for the study of diabetes (EASD)","volume":"65","author":"Davies","year":"2022","journal-title":"Diabetologia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/S2213-8587(14)70161-5","article-title":"Trends in lifetime risk and years of life lost due to diabetes in the USA, 1985-2011: a modelling study","volume":"2","author":"Gregg","year":"2014","journal-title":"Diabetes & Endocrinol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.diabres.2013.11.002","article-title":"Global estimates of diabetes prevalence for 2013 and projections for 2035","volume":"103","author":"Guariguata","year":"2014","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B6","doi-asserted-by":"publisher","first-page":"CD008143","DOI":"10.1002\/14651858.CD008143.pub3","article-title":"Targeting intensive glycaemic control versus targeting conventional glycaemic control for type 2 diabetes mellitus","author":"Hemmingsen","year":"2013","journal-title":"Cochrane database Syst. Rev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1056\/NEJMoa0806470","article-title":"10-year follow-up of intensive glucose control in type 2 diabetes","volume":"359","author":"Holman","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B8","doi-asserted-by":"crossref","unstructured":"Integrated addendum to ICH E6(R1): guideline for good clinical practice E6(R2)2016","DOI":"10.1097\/HS9.0000000000000006"},{"key":"B9","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s40261-013-0096-7","article-title":"A comparison of the steady-state pharmacokinetic and pharmacodynamic profiles of 100 and 200 U\/mL formulations of ultra-long-acting insulin degludec","volume":"33","author":"Korsatko","year":"2013","journal-title":"Clin. drug Investig."},{"key":"B10","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1016\/S2213-8587(14)70172-X","article-title":"The US diabetes epidemic: tip of the iceberg","volume":"2","author":"Lipscombe","year":"2014","journal-title":"Diabetes & Endocrinol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"98","DOI":"10.34172\/hpp.2020.18","article-title":"Prevalence and incidence of type 1 diabetes in the world: a systematic review and meta-analysis","volume":"10","author":"Mobasseri","year":"2020","journal-title":"Health Promot. Perspect."},{"key":"B12","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/S0140-6736(98)07019-6","article-title":"Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group","volume":"352","year":"1998","journal-title":"Lancet (London, Engl."},{"key":"B13","unstructured":"Bioavailability and bioequivalence requirements. 21 CFR 21 Part 3202009"},{"key":"B14","unstructured":"Pharmacology review(s) for Tresiba2015"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"JAMA"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1294810\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T02:04:10Z","timestamp":1703815450000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1294810\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,22]]},"references-count":15,"alternative-id":["10.3389\/fphar.2023.1294810"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1294810","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,22]]},"article-number":"1294810"}}