Introduction <p>IcoSema is under development as a once-weekly injectable combination therapy of icodec (basal insulin) and semaglutide (glucagon-like peptide&#xa0;1 receptor agonist). This study assessed the pharmacokinetic characteristics of icodec and semaglutide following IcoSema administration vs. administration of icodec and semaglutide alone in Chinese individuals with type&#xa0;2 diabetes (T2D).</p> Methods <p>In a randomized, double-blind, three-period crossover study, 20&#xa0;Chinese individuals with T2D (18–64&#xa0;years, body mass index 18.5–34.9&#xa0;kg/m<sup>2</sup>, glycated hemoglobin ≤ 9.0%) were given single subcutaneous administrations of IcoSema, icodec, or semaglutide separated by 6–9&#xa0;weeks. Blood was drawn for pharmacokinetic measurement until 840&#xa0;h post dose.</p> Results <p>Combining icodec with semaglutide had no impact on icodec pharmacokinetics. The ratio and 90% confidence interval of IcoSema/icodec was 1.04 [0.99;1.08] for area under the curve from zero to last quantifiable observation (AUC<sub>0–<i>t</i></sub>) and 1.02 [0.96;1.09] for maximum concentration (<i>C</i><sub>max</sub>), i.e., within the bioequivalence acceptance interval of 0.80–1.25. Likewise, combining semaglutide with icodec had no impact on semaglutide AUC<sub>0–<i>t</i></sub> (IcoSema/semaglutide 0.99 [0.94;1.05]). However, semaglutide <i>C</i><sub>max</sub> was higher for IcoSema vs. semaglutide alone (1.42 [1.31;1.53]) and occurred earlier for IcoSema (12 vs. 66&#xa0;h). All three treatments were safe with no differences in frequency, severity or outcome of adverse events, or relationship to study product.</p> Conclusion <p>In Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema.</p> Trial Registration <p>ClinicalTrials.gov identifier, NCT05435677.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Pharmacokinetic Characteristics of a Once-Weekly Combination Therapy of Insulin Icodec and Semaglutide Versus Its Separate Components in Chinese Individuals with Type 2 Diabetes

  • Fangfang Wang,
  • Zijian Luan,
  • Raluca Maltesen,
  • Asbjørn T. Reenberg,
  • Lisbet Westergaard,
  • Dongyang Liu

摘要

Introduction

IcoSema is under development as a once-weekly injectable combination therapy of icodec (basal insulin) and semaglutide (glucagon-like peptide 1 receptor agonist). This study assessed the pharmacokinetic characteristics of icodec and semaglutide following IcoSema administration vs. administration of icodec and semaglutide alone in Chinese individuals with type 2 diabetes (T2D).

Methods

In a randomized, double-blind, three-period crossover study, 20 Chinese individuals with T2D (18–64 years, body mass index 18.5–34.9 kg/m2, glycated hemoglobin ≤ 9.0%) were given single subcutaneous administrations of IcoSema, icodec, or semaglutide separated by 6–9 weeks. Blood was drawn for pharmacokinetic measurement until 840 h post dose.

Results

Combining icodec with semaglutide had no impact on icodec pharmacokinetics. The ratio and 90% confidence interval of IcoSema/icodec was 1.04 [0.99;1.08] for area under the curve from zero to last quantifiable observation (AUC0–t) and 1.02 [0.96;1.09] for maximum concentration (Cmax), i.e., within the bioequivalence acceptance interval of 0.80–1.25. Likewise, combining semaglutide with icodec had no impact on semaglutide AUC0–t (IcoSema/semaglutide 0.99 [0.94;1.05]). However, semaglutide Cmax was higher for IcoSema vs. semaglutide alone (1.42 [1.31;1.53]) and occurred earlier for IcoSema (12 vs. 66 h). All three treatments were safe with no differences in frequency, severity or outcome of adverse events, or relationship to study product.

Conclusion

In Chinese individuals with T2D, icodec pharmacokinetics and semaglutide total exposure are unaffected when combining icodec and semaglutide in IcoSema. However, maximum semaglutide concentration is higher and occurs earlier with IcoSema. This information may help to ensure suitable dose recommendations for IcoSema.

Trial Registration

ClinicalTrials.gov identifier, NCT05435677.