English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

P195 Clomethiazole (CMZ; ‘Zendra’) is a neuroprotective drug  that enhances GABA-A receptor activity. Two clinical trials in stroke  patients (pts) were performed: 92CM01 (n=17) and CLASS (CLomethiazole  Acute Stroke Study; n=678 on CMZ). In CLASS, a post-hoc analysis showed  that CMZ appeared to improve outcome in pts with clinical signs  suggestive of a large stroke. Dosing for the pivotal trial, CLASS-I,  was based on information from these previous studies. In 92CM01, a  loading dose of 6 mg/kg given over 15 min followed by a maintenance  dose of 69 mg/kg to 24 h was the maximum CMZ dose that could be  given without excessive sedation. In this study, plasma sampling from  each pt allowed for individual kinetic modelling. In CLASS, the same  dose regimen was used. One sample for drug analysis was taken from each  pt at the end of the 24-h infusion. In total, 619 CLASS pts were  eligible for a population kinetic evaluation. The clearance estimates  in both studies were in the same range. Therefore, the pharmacokinetic  parameter estimates from study 92CM01 could be used to simulate the  plasma concentrations according to a 2-compartment model for different  dosing regimens. According to the protocols, CMZ infusion should be  temporarily interrupted if pts become excessively sedated. In CLASS,  there were 218 infusion interruptions in 158 pts. CMZ kinetics did not  differ between pts who had interruptions and those who did not. There  was a delay in the occurrence of excessive sedation, with the majority  of interruptions seen between 10 and 24 h. Pts with clinical signs  suggesting a large stroke were particularly susceptible to sedation in  CLASS, a new dose regimen was needed to reduce excessive sedation in  these pts. For CLASS-I the adjusted dosage regimen was calculated as a  total CMZ dose of 68 mg/kg, given as a 15 min loading dose, followed by  two maintenance doses over 7.75 and 16 h respectively. This should  avoid high plasma concentrations during the second half of the infusion  period. Taking into account treatment interruptions, CLASS-I pts are  predicted to receive an average dose of 63 mg/kg, the same as was  actually received by such pts in CLASS.‘Zendra’ is a  trademark, the property of the AstraZeneca group of  companies

Rationale for the selection of the dose regimen of ‘Zendra’ used in the CLASS-I study