Delving into the Latest Updates on Oxiracetam with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Oxiracetam (INN)

+ [9]

Target

GRIA2

Mechanism

GRIA2 positive allosteric modulator(glutamate ionotropic receptor AMPA type subunit 2 positive allosteric modulator)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Brain InjuriesDementiaMemory Disorders

Inactive Indication

Perioperative ischaemiaTrichothiodystrophy Syndromes

Originator Organization-

Active Organization

Hunan Jianlang Pharmaceutical Co. Ltd.

CSPC Ouyi Pharmaceutical Co., Ltd.

KOREAN DRUG Co., Ltd.

Inactive Organization

Harbin Medisan Pharmaceutical Co., Ltd.

Chongqing Dongze Medicine Technology Development Co., Ltd.

Drug Highest PhaseApproved

First Approval Date

IT (01 Jan 1987)

Regulation-

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Structure

Molecular FormulaC6H10N2O3

InChIKeyIHLAQQPQKRMGSS-UHFFFAOYSA-N

CAS Registry62613-82-5

AbstractObjectivesPatients with traumatic brain injury (TBI) often suffer memory and cognitive impairments, and oxiracetam‐like drugs are considered to have a positive impact on these symptoms potentially. However, the efficacy and safety of L‐oxiracetam and oxiracetam in TBI patients have not been sufficiently investigated.MethodsThe study adopts a multicenter, randomized, double‐blind, parallel‐group, phase 3 clinical trial design in 74 centers across 51 hospitals in China. A total of 590 TBI patients meeting criteria will be randomly allocated into three groups in a 2:2:1 ratio: L‐oxiracetam group, oxiracetam group, and placebo group. The treatment period is 14 days, with a follow‐up period of 90 days. The primary outcome measure is the change in the Loewenstein Occupational Therapy Cognitive Assessment score at 90 days after treatment. Secondary outcomes include changes in other cognitive assessments, neurological function, activities of daily living, and safety assessments.DiscussionThere is no robust evidence to suggest that L‐oxiracetam and oxiracetam can enhance memory and cognitive function in patients with mild to moderate TBI. This study has the potential to answer this crucial clinical question.Trial registrationchinadrugtrials.org.cn, identifier CTR20192539; ClinicalTrials.gov, identifier NCT04205565.

01 Feb 2024·Journal of Pharmaceutical and Biomedical Analysis

Development and validation of a chiral UPLC-MS/MS method for quantifying S-Oxiracetam and R-Oxiracetam in human plasma, urine and feces: Application to a phase-I clinical pharmacokinetic study

Article

Author: Li, Ning ; Wang, Yao ; Sha, Yutong ; Chen, Huili ; Zhao, Di ; Chen, Xijing ; Su, Shengdi ; Li, Jia ; Han, Luyao ; Liu, Yuhan

A chiral UPLC-MS/MS method was developed and validated to determine oxiracetam enantiomers in human plasma, urine, and feces. The R-Oxiracetam and S-Oxiracetam were quantified using a CHIRALPAK ®AD3 column at 25 ℃, and the resolution was greater than 3.2. The S-Oxiracetam is the eutomer that isresponsible for the treatment of various brain damage. Isocratic elution was conducted at a flow rate of 0.9 mL/min for 6 min using the mixture of methanol and acetonitrile (methanol:acetonitrile, 15:85) containing 0.3‰ formic acid. The methods showed linearity at the range of 0.5-100 µg/mL for each oxiracetam enantiomer. A comprehensive validation process was carried out, covering aspects including linearity, selectivity, carryover, accuracy, precision, interferences, matrix effect, recovery, dilution integrity and stability in matrix and solution. The validated methods were successfully applied to quantifying R-Oxiracetam and S-Oxiracetam in human plasma, urine, and feces of 12 healthy subjects treated with either a single dose of 2 g S-Oxiracetam injection or 4 g Oxiracetam injection in a phase-I clinical trial. There was no significant difference for plasma pharmacokinetic parameters of S-Oxiracetam between the two regimens (P＞0.05). The S-Oxiracetam and Oxiracetam were primarily eliminated through urine in their original form, with cumulative excretion rates of 92.16% and 85.92%, respectively, within 24 h after administration. Enantiomers interconversion was not observed in the plasma, urine, or feces. The results of this study suggest that replacing 4 g Oxiracetam injection with 2 g S-Oxiracetam injection could offer clinical benefits by lowering the dosage and mitigating potential risks, based on the pharmacokinetic characteristics.

01 Jan 2024·European Journal of Pharmaceutical Sciences

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

Article

Author: Tang, Chengyong ; Wan, Lei ; Tao, Yi ; Zhang, Ting ; Zhu, Mingxue ; Pu, Junliang

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.METHODSA 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).RESULTSAEs 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.

100 Deals associated with Oxiracetam

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External Link

KEGG	Wiki	ATC	Drug Bank
D07346	Oxiracetam	N06BX07	DB13601

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Brain Injuries	CN	Hunan Jianlang Pharmaceutical Co. Ltd.	28 Feb 1997
Dementia	CN	Hunan Jianlang Pharmaceutical Co. Ltd.	28 Feb 1997
Memory Disorders	CN	CSPC Ouyi Pharmaceutical Co., Ltd.	28 Feb 1997

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Perioperative ischaemia	Preclinical	CN	Harbin Medisan Pharmaceutical Co., Ltd.	04 Nov 2019
Trichothiodystrophy Syndromes	Preclinical	CN	Harbin Medisan Pharmaceutical Co., Ltd.	04 Nov 2019