Safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in Chinese healthy volunteers: A randomized, double-blind, controlled phase I study. 2024

Ting Zhang, and Yi Tao, and Junliang Pu, and Mingxue Zhu, and Lei Wan, and Chengyong Tang
Phase I Clinical Trial Center, Bishan Hospital of Chongqing, Bishan hospital of Chongqing medical university, Chongqing, 402760, China.

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 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. CONCLUSIONS (S)-oxiracetam was safe and tolerated with favorable pharmacokinetic profiles at all study doses, providing dosing evidence for further efficacy evaluation.

UI MeSH Term Description Entries
D011759 Pyrrolidines Compounds also known as tetrahydropyridines with general molecular formula (CH2)4NH. Tetrahydropyridine,Tetrahydropyridines
D002681 China A country spanning from central Asia to the Pacific Ocean. Inner Mongolia,Manchuria,People's Republic of China,Sinkiang,Mainland China
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000095225 East Asian People East Asians,Eastern Asian People,Eastern Asians,Far East Asians,Chinese,Japanese,Koreans,Asian People, East,Asian People, Eastern,Asian, East,Asian, Eastern,Asian, Far East,East Asian,East Asian Peoples,Eastern Asian,Eastern Asian Peoples,Far East Asian,People, East Asian,People, Eastern Asian
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D018697 Nootropic Agents Drugs used to specifically facilitate learning or memory, particularly to prevent the cognitive deficits associated with dementias. These drugs act by a variety of mechanisms. Anti-Dementia Agent,Antidementia Agent,Cognitive Enhancer,Cognitive Enhancers,Nootropic,Nootropic Agent,Nootropic Drug,Procognitive Agent,Anti-Dementia Agents,Antidementia Agents,Nootropic Drugs,Nootropics,Procognitive Agents,Agent, Anti-Dementia,Agent, Antidementia,Agent, Nootropic,Agent, Procognitive,Agents, Anti-Dementia,Agents, Antidementia,Agents, Nootropic,Agents, Procognitive,Anti Dementia Agent,Anti Dementia Agents,Drug, Nootropic,Drugs, Nootropic,Enhancer, Cognitive,Enhancers, Cognitive
D019540 Area Under Curve A statistical means of summarizing information from a series of measurements on one individual. It is frequently used in clinical pharmacology where the AUC from serum levels can be interpreted as the total uptake of whatever has been administered. As a plot of the concentration of a drug against time, after a single dose of medicine, producing a standard shape curve, it is a means of comparing the bioavailability of the same drug made by different companies. (From Winslade, Dictionary of Clinical Research, 1992) AUC,Area Under Curves,Curve, Area Under,Curves, Area Under,Under Curve, Area,Under Curves, Area
D064368 Healthy Volunteers Persons with no known significant health problems who are recruited to participate in research to test a new drug, device, or intervention as controls for a patient group. (from http://clinicalcenter.nih.gov/recruit/volunteers.html, accessed 2/14/2013) Healthy Participants,Healthy Subjects,Human Volunteers,Normal Volunteers,Healthy Participant,Healthy Subject,Healthy Volunteer,Human Volunteer,Normal Volunteer,Participant, Healthy,Participants, Healthy,Subject, Healthy,Subjects, Healthy,Volunteer, Healthy,Volunteer, Human,Volunteer, Normal,Volunteers, Human,Volunteers, Normal

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