L-oxiracetam
Intravenous L-oxiracetam improved one cognitive battery during 90-day recovery from acute traumatic brain injury in a 590-person Chinese trial. Daily function and global recovery did not improve, and oral healthy-person benefit has never been tested.
Investigational single-enantiomer racetam
- LOCATE used IV L-oxiracetam 4 g/day for 14 inpatient days, usually starting within 72 hours of injury.
- At day 90, LOTCA improvement exceeded placebo by 8.97 points; MMSE, global recovery and activities of daily living were null.
- 146/590 participants missed the day-90 visit.
- Healthy oral and IV studies measured pharmacokinetics and short-term safety, not cognition.
What exactly did LOCATE test?
L-oxiracetam is the S enantiomer of racemic oxiracetam. LOCATE tested a pharmaceutical IV product at 4 g/day for 14 days after acute traumatic brain injury.
The study randomized L-oxiracetam, racemic oxiracetam and placebo as separate arms at different doses. The IV result does not establish efficacy for oral powder, chronic use or a person without brain injury.
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R, . Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceSafety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study.
Primary human pharmacokinetic study
Zhang T, Tao Y, Pu J, Zhu M, Wan L, Tang C. Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2024. DOI 10.1016/j.ejps.2023.106621.
Oral (S)-oxiracetam reached peak concentrations at 0.75 to 1 hour fasting and three hours fed; reported half-lives were 6.12 to 6.60 hours. Adverse events were mild or moderate. Mild accumulation followed seven days of repeated dosing.
- Participants / model
- Healthy Chinese volunteers; the abstract does not state enrollment
- Follow-up
- Single exposures and seven days of repeated dosing
- Study design
- Randomized double-blind controlled dose-escalation phase I study
This oral phase I study is distinct from intravenous efficacy treatment after traumatic brain injury.
Read the original sourceChinese intravenous PK study, 2021
Primary human pharmacokinetic study
Liang D et al. Eur J Drug Metab Pharmacokinet. 2021;46:793 to 805. PMID 34549388. DOI 10.1007/s13318-021-00718-9.
52 volunteers completed the three-part study; one mild possibly related event and no serious events were reported. Little accumulation was observed over seven days.
- Participants / model
- 52 healthy volunteers completed: 30 dose escalation, 12 crossover, ten repeated infusion
- Follow-up
- Single infusions or seven days of repeated infusion
- Study design
- Three-part intravenous PK and tolerability program; S-oxiracetam versus racemate crossover in one part
The abstract does not establish long-term safety, treatment efficacy, or equivalence to oral dosing. Some authors were affiliated with the developer.
Read the original sourceHow much did cognition improve after traumatic brain injury?
At day 90, adjusted LOTCA improvement was 20.45 points with L-oxiracetam and 11.47 with placebo. The prespecified difference was 8.97 points (95% CI 5.69 to 12.26; p<0.001; Cohen d 0.48).
LOCATE randomized 590 adults at 51 Chinese hospitals: 235 received L-oxiracetam, 236 racemic oxiracetam and 119 placebo. More than 90% had mild rather than moderate TBI, and all groups received standard care.
The placebo group gained 11.47 points, so spontaneous recovery and repeat testing explain much of the raw improvement. The treatment estimate is the prespecified between-group difference.
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R, . Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceDid the ordinary oxiracetam arm also work?
LOCATE did not report a prespecified racemic-oxiracetam-versus-placebo efficacy comparison. Its positive conclusion belongs to L-oxiracetam.
L-oxiracetam exceeded racemic oxiracetam by 4.54 LOTCA points (95% CI 1.85 to 7.23). Subtracting the printed racemate and placebo arm means after the fact does not create a tested treatment comparison.
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R, . Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceDid patients become more independent or recover globally?
The trial did not show better activities of daily living, global recovery or most secondary cognitive measures.
MMSE was null at days 14 and 90. MoCA differed by 1.11 points at day 90 but not day 14. Glasgow Coma Scale, favorable GOS-E and Barthel Index were null through day 90.
A cognitive-battery signal can be real without producing a measured daily-function benefit.
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R, . Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceWhat do the mouse studies add?
Five days of IV pretreatment improved selected learning measures in mice after scopolamine, sodium-nitrite or ethanol impairment.
Selected groups also had more brain acetylcholine and less acetylcholinesterase activity. The mice were chemically impaired and received very high weight-based IV exposures; this does not define an oral human dose or healthy-memory effect.
左旋奥拉西坦对小鼠学习记忆功能障碍的影响 / S-oxiracetam in mouse memory-impairment models
Preclinical primary mouse study
樊文香, 李晓敏, 徐驰 / Fan W, Li X, Xu C. 中国药科大学学报. 2021. DOI 10.11665/j.issn.1000-5048.20210111.
Selected treatment groups improved memory-task measures and altered brain acetylcholine and acetylcholinesterase.
- Participants / model
- Male ICR mice; 50 per chemical-impairment model, ten per group
- Follow-up
- Five days of intravenous pretreatment, followed by learning and memory tests
- Study design
- Weight-randomized experiments in scopolamine, sodium-nitrite and ethanol impairment models
- Funding
- National Natural Science Foundation of China grant 81701313 and Fundamental Research Funds for the Central Universities grant 2242020K40175; drug supplied by Shandong Luoxin Pharmaceutical.
No blinding described, no racemic comparator and no clinical Alzheimer disease population. The final sentence conflicts with the results and abstract about acetylcholine: the reported results indicate higher ACh and lower AChE activity in selected groups.
Read the original sourceWhat happens after oral dosing?
In healthy Chinese volunteers, oral S-oxiracetam peaked at 0.75 to 1 hour fasting and around three hours with food; reported half-life was 6.12 to 6.60 hours.
The oral phase 1 used single ascending doses and seven days of repeated dosing. It reported mild or moderate events and mild accumulation, but no cognitive outcome.
A separate IV study found no enantiomer interconversion and recovered most drug unchanged in urine within 24 hours. These studies establish exposure, not therapeutic equivalence.
Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study.
Primary human pharmacokinetic study
Zhang T, Tao Y, Pu J, Zhu M, Wan L, Tang C. Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2024. DOI 10.1016/j.ejps.2023.106621.
Oral (S)-oxiracetam reached peak concentrations at 0.75 to 1 hour fasting and three hours fed; reported half-lives were 6.12 to 6.60 hours. Adverse events were mild or moderate. Mild accumulation followed seven days of repeated dosing.
- Participants / model
- Healthy Chinese volunteers; the abstract does not state enrollment
- Follow-up
- Single exposures and seven days of repeated dosing
- Study design
- Randomized double-blind controlled dose-escalation phase I study
This oral phase I study is distinct from intravenous efficacy treatment after traumatic brain injury.
Read the original sourceChinese intravenous PK study, 2021
Primary human pharmacokinetic study
Liang D et al. Eur J Drug Metab Pharmacokinet. 2021;46:793 to 805. PMID 34549388. DOI 10.1007/s13318-021-00718-9.
52 volunteers completed the three-part study; one mild possibly related event and no serious events were reported. Little accumulation was observed over seven days.
- Participants / model
- 52 healthy volunteers completed: 30 dose escalation, 12 crossover, ten repeated infusion
- Follow-up
- Single infusions or seven days of repeated infusion
- Study design
- Three-part intravenous PK and tolerability program; S-oxiracetam versus racemate crossover in one part
The abstract does not establish long-term safety, treatment efficacy, or equivalence to oral dosing. Some authors were affiliated with the developer.
Read the original sourceWhat did LOCATE show about risk and follow-up?
Overall adverse-event rates were similar, but treatment-related events were more frequent with racemic oxiracetam than with L-oxiracetam or placebo.
Any adverse event occurred in 155/235 L-oxiracetam, 157/236 racemate and 80/119 placebo recipients. Treatment-related events occurred in 22/235, 41/236 and 11/119 (overall p=0.049). No serious event was judged treatment-related.
The controlled treatment window was 14 days. The study cannot settle chronic oral use, pregnancy, renal impairment or polypharmacy. A rat distribution study detected S-oxiracetam in fetal tissues after repeated IV exposure; that is placental-transfer evidence in rats, not a quantified human pregnancy risk.
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R, . Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceSafety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study.
Primary human pharmacokinetic study
Zhang T, Tao Y, Pu J, Zhu M, Wan L, Tang C. Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2024. DOI 10.1016/j.ejps.2023.106621.
Oral (S)-oxiracetam reached peak concentrations at 0.75 to 1 hour fasting and three hours fed; reported half-lives were 6.12 to 6.60 hours. Adverse events were mild or moderate. Mild accumulation followed seven days of repeated dosing.
- Participants / model
- Healthy Chinese volunteers; the abstract does not state enrollment
- Follow-up
- Single exposures and seven days of repeated dosing
- Study design
- Randomized double-blind controlled dose-escalation phase I study
This oral phase I study is distinct from intravenous efficacy treatment after traumatic brain injury.
Read the original sourceChinese intravenous PK study, 2021
Primary human pharmacokinetic study
Liang D et al. Eur J Drug Metab Pharmacokinet. 2021;46:793 to 805. PMID 34549388. DOI 10.1007/s13318-021-00718-9.
52 volunteers completed the three-part study; one mild possibly related event and no serious events were reported. Little accumulation was observed over seven days.
- Participants / model
- 52 healthy volunteers completed: 30 dose escalation, 12 crossover, ten repeated infusion
- Follow-up
- Single infusions or seven days of repeated infusion
- Study design
- Three-part intravenous PK and tolerability program; S-oxiracetam versus racemate crossover in one part
The abstract does not establish long-term safety, treatment efficacy, or equivalence to oral dosing. Some authors were affiliated with the developer.
Read the original sourceChinese placental-distribution study, 2017
Primary preclinical analytical study
Shen YY, Yue P, Qiao HQ. Chinese Journal of Pharmaceutical Analysis. 2017;37(6):1056 to 1062. DOI 10.16155/j.0254-1793.2017.06.18.
S-oxiracetam was detected in fetal tissues after repeated intravenous exposure in pregnant rats, supporting placental transfer.
- Participants / model
- 16 pregnant Sprague-Dawley rats, four per group
- Follow-up
- Gestation days 6 to 20
- Study design
- Randomized control and three exposure groups; tissue collection five minutes after the final dose
A tissue-distribution study, not a measurement of malformation risk or human pregnancy safety. The discussion and methods disagree on solvent proportions; no assay recipe is reproduced. Study material was described as a Shandong Luoxin product.
Read the original sourceHow complete was the day-90 result?
146/590 randomized participants lacked the day-90 visit: 49/235 L-oxiracetam, 62/236 racemate and 35/119 placebo.
The investigators used an intention-to-treat model and reported a directionally consistent per-protocol analysis. Nearly one quarter missing the primary visit still limits precision. Blinding success, symptom validity, mood, sleep and headache were not assessed.
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R, . Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceIs L-oxiracetam an approved oral nootropic?
Chinese records support a phase 3 trial and trial authorization, but they do not establish current marketing approval or an oral cognitive-enhancement indication.
The cited evidence includes no independent replication, healthy-rested cognition trial, dementia-prevention result, sleep-loss study, strength trial, or longevity outcome.
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R, . Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original sourceStudies and sources
Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial.
Primary human study
Liu T, Wang J, Zhao Z, Jiang W, Zhang M, Yu Y, Liu Y, Liu M, Chen L, Zhang H, Hong Y, Li B, Yu R, Ji H, Mi L, Zhao B, Lv C, Liu C, Zhang J, Jiang R, . Efficacy and safety of L-oxiracetam on cognitive function in patients with traumatic brain injury: a multicentre, randomised, double-blind, phase 3 clinical trial. Signal transduction and targeted therapy. 2025. DOI 10.1038/s41392-025-02492-5
L-oxiracetam improved the primary cognitive-test endpoint against placebo; the racemate is a separate comparator.
- Participants / model
- 590 participants with mild-to-moderate traumatic brain injury at 51 Chinese hospitals
- Study design
- Randomized double-blind phase 3 trial; 14 treatment days and 90-day follow-up
The primary efficacy comparison was L-oxiracetam versus placebo. Trial authorization is not marketing approval.
Read the original source左旋奥拉西坦对小鼠学习记忆功能障碍的影响 / S-oxiracetam in mouse memory-impairment models
Preclinical primary mouse study
樊文香, 李晓敏, 徐驰 / Fan W, Li X, Xu C. 中国药科大学学报. 2021. DOI 10.11665/j.issn.1000-5048.20210111.
Selected treatment groups improved memory-task measures and altered brain acetylcholine and acetylcholinesterase.
- Participants / model
- Male ICR mice; 50 per chemical-impairment model, ten per group
- Follow-up
- Five days of intravenous pretreatment, followed by learning and memory tests
- Study design
- Weight-randomized experiments in scopolamine, sodium-nitrite and ethanol impairment models
- Funding
- National Natural Science Foundation of China grant 81701313 and Fundamental Research Funds for the Central Universities grant 2242020K40175; drug supplied by Shandong Luoxin Pharmaceutical.
No blinding described, no racemic comparator and no clinical Alzheimer disease population. The final sentence conflicts with the results and abstract about acetylcholine: the reported results indicate higher ACh and lower AChE activity in selected groups.
Read the original sourceSafety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study.
Primary human pharmacokinetic study
Zhang T, Tao Y, Pu J, Zhu M, Wan L, Tang C. Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2024. DOI 10.1016/j.ejps.2023.106621.
Oral (S)-oxiracetam reached peak concentrations at 0.75 to 1 hour fasting and three hours fed; reported half-lives were 6.12 to 6.60 hours. Adverse events were mild or moderate. Mild accumulation followed seven days of repeated dosing.
- Participants / model
- Healthy Chinese volunteers; the abstract does not state enrollment
- Follow-up
- Single exposures and seven days of repeated dosing
- Study design
- Randomized double-blind controlled dose-escalation phase I study
This oral phase I study is distinct from intravenous efficacy treatment after traumatic brain injury.
Read the original sourceChinese intravenous PK study, 2021
Primary human pharmacokinetic study
Liang D et al. Eur J Drug Metab Pharmacokinet. 2021;46:793 to 805. PMID 34549388. DOI 10.1007/s13318-021-00718-9.
52 volunteers completed the three-part study; one mild possibly related event and no serious events were reported. Little accumulation was observed over seven days.
- Participants / model
- 52 healthy volunteers completed: 30 dose escalation, 12 crossover, ten repeated infusion
- Follow-up
- Single infusions or seven days of repeated infusion
- Study design
- Three-part intravenous PK and tolerability program; S-oxiracetam versus racemate crossover in one part
The abstract does not establish long-term safety, treatment efficacy, or equivalence to oral dosing. Some authors were affiliated with the developer.
Read the original sourceChinese placental-distribution study, 2017
Primary preclinical analytical study
Shen YY, Yue P, Qiao HQ. Chinese Journal of Pharmaceutical Analysis. 2017;37(6):1056 to 1062. DOI 10.16155/j.0254-1793.2017.06.18.
S-oxiracetam was detected in fetal tissues after repeated intravenous exposure in pregnant rats, supporting placental transfer.
- Participants / model
- 16 pregnant Sprague-Dawley rats, four per group
- Follow-up
- Gestation days 6 to 20
- Study design
- Randomized control and three exposure groups; tissue collection five minutes after the final dose
A tissue-distribution study, not a measurement of malformation risk or human pregnancy safety. The discussion and methods disagree on solvent proportions; no assay recipe is reproduced. Study material was described as a Shandong Luoxin product.
Read the original sourceWhy is L-oxiracetam in B tier?
B applies to one phase 3 result: short-course IV treatment after acute mild-to-moderate traumatic brain injury. The trial did not establish oral nootropic use, better cognition in healthy people, improved daily independence, dementia prevention or longevity.