Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study.

Background and Objective: (S)-oxiracetam is the major active enantiomer of oxiracetam, which is being developed for dementia. This trial was designed to evaluate the safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in healthy Chinese volunteers.
Methods: A randomized, controlled, double-blind and dose-escalation design was used in this Phase I trial, which consisted of a single-ascending-dose (SAD) study (400-2000 mg) and a multiple-ascending-dose (MAD) study (400-1600 mg). Blood, urine and feces samples were collected for pharmacokinetic analysis. Safety was evaluated by monitoring adverse events (AEs).
Results: AEs in both studies were mild or moderate in severity and dose-independent. In the SAD study, no chiral transformation was observed. 55.03% and 36.16% of (S)-oxiracetam was excreted unchanged in urine and feces, respectively. Exposures exhibited dose-proportional increases over the range of 400 to 1600 mg but almost unchanged from 1600 to 2000 mg. (S)-oxiracetam was absorbed rapidly, reaching a peak at 0.75-1.00 h, and t _1/2 was 6.12-6.60 h. Food had no effect on AUC, but prolonged T _max to 3.00 h. In the MAD study, steady-state was observed on day 5. Mild accumulations were observed after 7 days of repeated dosing.
Conclusion: (S)-oxiracetam was safe and tolerated with favorable pharmacokinetic profiles at all study doses, providing dosing evidence for further efficacy evaluation.
Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest that are directly relevant to the content of this article.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)