AZD8233 antisense oligonucleotide targeting PCSK9 does not prolong QT interval
| العنوان: | AZD8233 antisense oligonucleotide targeting PCSK9 does not prolong QT interval |
|---|---|
| المؤلفون: | Dinko Rekić, Ivan Azarov, Jane Knöchel, Victor Sokolov, Catarina Nilsson, Linda Wernevik, David Han, Tina Rydén‐Bergsten, Ahmad Ebrahimi, Corina Dota, Björn Carlsson |
| المصدر: | British Journal of Clinical Pharmacology. 88:4839-4844 |
| بيانات النشر: | Wiley, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Adult, Male, Pharmacology, Cross-Over Studies, Dose-Response Relationship, Drug, Oligonucleotides, Oligonucleotides, Antisense, Electrocardiography, Long QT Syndrome, Double-Blind Method, Heart Rate, Humans, Pharmacology (medical), Subtilisins, Proprotein Convertase 9 |
| الوصف: | AZD8233 is a proprotein convertase subtilisin/kexin type 9 (PCSK9) antisense oligonucleotide under development for treatment of hypercholesterolaemia. A prespecified concentration-QT analysis was performed based on data from a single ascending dose study that was prospectively designed to act as a TQT study substitute.Subcutaneous single doses ranging from 4 to 120 mg were evaluated in 73 adult healthy male subjects. Time-matched 12-lead digital ECG and plasma concentrations (n = 15) were measured at baseline and up to 48 hours after dose in each subject. The analysis was performed using a linear mixed effect model, where change from baseline QTc (ΔQTc) was a dependent variable and time-matched AZD8233 concentration was an independent variable.The high clinical exposure scenario was defined as 1.7-fold the expected CAs the effect on ΔΔQTcF is below the threshold for regulatory concern (10 ms), it can be concluded that AZD8233 does not induce QTcF prolongation at the high clinical exposure scenario. |
| تدمد: | 1365-2125 0306-5251 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::134aac677ccd322d75dbf14e4da7d520 https://doi.org/10.1111/bcp.15425 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....134aac677ccd322d75dbf14e4da7d520 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13652125 03065251 |
|---|