%0 Randomized Controlled Trial
%T Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study.
%A Zhang T
%A Tao Y
%A Pu J
%A Zhu M
%A Wan L
%A Tang C
%J Eur J Pharm Sci
%V 192
%N 0
%D 2024 Jan 1
%M 37898393
%F 5.112
%R 10.1016/j.ejps.2023.106621
%X <B>OBJECTIVE: </B>(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.<BR><B>METHODS: </B>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).<BR><B>RESULTS: </B>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 t1/2 was 6.12-6.60 h. Food had no effect on AUC, but prolonged Tmax 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.<BR><B>CONCLUSIONS: </B>(S)-oxiracetam was safe and tolerated with favorable pharmacokinetic profiles at all study doses, providing dosing evidence for further efficacy evaluation.