Comparative Study of the Pharmacokinetics, Efficacy and Safety of ET-26 in Elderly and Non-Elderly Subjects: The Results of a Phase I Clinical Trial

Fan Yang¹Jing Sun¹Pan-Pan Ye¹Wen-Shuo Lv¹Li-Ze Li²Bao-Zhong Zhao²Johannes Nicolaas Van Den Anker^3,4,5Yi Zheng^1*Bo-Wen Ke^6*Xiaoran Yang^2*Wei Zhao^1*

• ¹Shandong University, Jinan, China
• ²Avanc Pharmaceutical Co., Ltd, Jinzhou, China
• ³Children's National Hospital, Washington, United States
• ⁴George Washington University, School of Medicine and Health Sciences, Washington, DC, United States
• ⁵University Children’s Hospital Basel, University of Basel, Basel, Switzerland
• ⁶West China Hospital of Sichuan University, Chengdu, China

Aim:To evaluate the pharmacokinetics, pharmacodynamics, and safety of the novel systemic intravenous anesthetic ET-26—an etomidate derivative designed to reduce adrenal suppression—in healthy elderly and non-elderly subjects. Methods: In this Phase I, single-center, non-randomized, open-label trial, 16 volunteers were enrolled: eight elderly (≥ 65 years, including ≥ 75 years) and eight non-elderly (18-64 years), matched for gender and body weight. Each received a standardized IV infusion of ET-26. Plasma concentrations were measured for plasma protein binding, Cmax, and AUC; time to loss of consciousness (LOC) and safety were assessed. Results: In 16 subjects (8 elderly/8 non-elderly), ET-26 showed higher exposure in the elderly (Cmax GMR 198.81%, 90%CI 126.51–312.45) and AUC0-∞ was 23.5% higher (90% CI: 107.6–141.9%) with comparable pharmacodynamics (median LOC time 1.933 min). Plasma protein binding remained stable (intergroup difference ≤1.0%). Drug-related TEAEs (37.5%) were mild and self-limiting. Conclusion: Despite elevated systemic exposure in elderly subjects, ET-26 demonstrates comparable efficacy and retains a favorable tolerability profile across age groups, eliminating the need for dose adjustments in elderly populations. Trial registration: CDE Clinical Trial Registry CTR20233784. Registered on 22 November 2023.