AUTHOR=Chen Ke-Guang , Zhang Ye-Hui , Ye Pan-Pan , Gao Xue-Hu , Song Lin-Lin , Zhou Hai-Yan , Li Qian , Zhao Fu-Rong , Shi Jin-Yi , Yang Xin-Mei , Shen Kai , Feng Sheng , Zhao Wei 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1294810

DOI=10.3389/fphar.2023.1294810

ISSN=1663-9812

ABSTRACT=<p><bold>Objectives:</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).</p><p><bold>Methods:</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<sub>max</sub>) and area under the concentration-time curve (AUC<sub>0–t</sub> and AUC<sub>0–∞</sub>) were used to evaluate relative bioavailability.</p><p><bold>Results:</bold> After a single dose at 0.4 U/kg, the median T<sub>max</sub> of INS068 was 12 h for both formulations, and the mean t<sub>1/2</sub> for T and R was 13.0 h and 12.6 h, respectively. The geometric means of C<sub>max</sub> and AUC<sub>0–∞</sub> were 3.99 nmol/L and 120 h·nmol/L for the T, and 4.05 nmol/L and 117 h·nmol/L for the R, respectively. The geometric mean ratios of C<sub>max</sub>, AUC<sub>0–t</sub> and AUC<sub>0–∞</sub> of T over R were 98.7% (90% CI: 92.7%–105.2%), 102.6% (90% CI: 100.0%–105.3%) and 102.8% (90% CI: 100.1%–105.5%).</p><p><bold>Conclusion:</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.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="http://clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">clinicaltrials.gov</ext-link>, identifier: NCT05336071</p>