Safety and tolerability of intrarectal perfluorodecalin for enteral ventilation in a first-in-human trial.

BACKGROUND

Enteral ventilation is an emerging approach that provides partial systemic oxygenation independent of pulmonary gas exchange, enabling lung rest. Perfluorodecalin, a clinically approved liquid with high oxygen solubility, is a promising vehicle for enteral oxygen delivery. The primary endpoint of this first-in-human trial was to assess the safety and tolerability of intrarectal perfluorodecalin administration.

METHODS

This was a phase 1, single-site, open-label, non-controlled, dose-escalation trial in 27 healthy adult males aged 20-45 years. Participants received a single intrarectal dose of non-oxygenated perfluorodecalin (escalating from 25 to 1,500 mL) retained for 60 min. Safety and tolerability were assessed through monitoring of adverse events, vital signs, clinical laboratory tests, and systemic perfluorodecalin exposure. A pharmacokinetic model using large-animal data was employed to predict potential oxygen transfer.

FINDINGS: No serious adverse events or dose-limiting toxicities occurred. Mild gastrointestinal symptoms, such as abdominal bloating and pain, were transient, dose dependent, and resolved without intervention. All clinical laboratory parameters, including liver and renal function markers, remained within normal limits. Perfluorodecalin concentrations were undetectable in blood (<1.0 μg/mL). The pharmacokinetic model predicted a dose-dependent oxygenation effect, consistent with a modest increase in peripheral oxygen saturation observed in the higher-dose group.

CONCLUSIONS

This first-in-human study demonstrates that intrarectal administration of non-oxygenated perfluorodecalin is safe, feasible, and well tolerated. These findings establish a critical safety foundation and support the continued development of enteral ventilation with fully oxygenated perfluorodecalin as an adjunctive strategy to support respiratory failure patients.

FUNDING: This work was funded by EVA Therapeutics, Inc.