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

TL;DR

A Phase I trial found that the new anesthetic ET-26 is safe and effective in both elderly and younger adults without needing dose changes.

Contribution

ET-26 shows comparable efficacy and safety in elderly and non-elderly subjects, eliminating the need for age-based dose adjustments.

Findings

ET-26 had higher exposure in elderly subjects (Cmax GMR 198.81%) but similar time to loss of consciousness.

Plasma protein binding was stable between age groups with no significant differences.

Drug-related adverse events were mild and self-limiting in both groups.

Abstract

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.

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.

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.

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.

http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml?keywords=CTR20233784, identifier CTR20233784.

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