التفاصيل البيبلوغرافية
| العنوان: |
A comprehensive analysis of liver safety across zibotentan oncology trials: knowledge of the past offers new perspectives on the present. |
| المؤلفون: |
Anna Fettiplace, Sherri Matis-Mitchell, Oleksandr Molodetskyi, Malin Söderbergh, Jan Oscarsson, Min Lin, Srivathsa Ravikiran, Martin Billger, Philip Ambery |
| سنة النشر: |
2024 |
| المجموعة: |
Smithsonian Institution: Figshare |
| مصطلحات موضوعية: |
Medicine, Cell Biology, Pharmacology, Immunology, Cancer, Science Policy, Mental Health, Infectious Diseases, Chemical Sciences not elsewhere classified, related adverse events, potential hy ’, placebo monotherapy arms, endothelin receptor antagonists, chronic kidney disease, 3 clinical trials, liver safety profile, analyze liver safety, cirrhosis ., clinical development, liver injury, used data, treated patients, six global, phase 2b, met criteria, mean ), descriptive statistics, comprehensive analysis, allowing exploration, 947 patients |
| الوصف: |
Endothelin receptor antagonists (ERAs) are associated with liver injury. We used data from previous oncology clinical trials to determine the liver safety profile of zibotentan, which is currently in clinical development (in combination with dapagliflozin) for chronic kidney disease and cirrhosis. Six global, double-blinded, phase 2b and 3 clinical trials from the zibotentan oncology development program were pooled to analyze liver safety. Descriptive statistics, proportion of liver-related adverse events, liver biochemistry parameter elevation, and shifts from baseline were analyzed, with individual case assessment. 1532 patients received zibotentan for 285 days (mean), and 1486 patients received placebo for 320 days (mean). The frequency of any hepatic disorder preferred term was similar across zibotentan monotherapy (22/947 patients, 2·3%) and placebo monotherapy arms (30/881 patients, 3·4%). A total of 4 (0·4%) patients receiving zibotentan monotherapy experienced ALT elevations > 5× ULN versus 8 (0·9%) receiving placebo. Of the 7 patients receiving zibotentan who met criteria for potential Hy’s Law, there were no cases of drug-induced liver injury. We found no evidence of zibotentan-related liver biochemistry changes among cancer-treated patients, suggesting that hepatotoxicity of ERAs is molecule-dependent, and allowing exploration of zibotentan for new indications. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/A_comprehensive_analysis_of_liver_safety_across_zibotentan_oncology_trials_knowledge_of_the_past_offers_new_perspectives_on_the_present_/25391415Test |
| DOI: |
10.6084/m9.figshare.25391415.v1 |
| الإتاحة: |
https://doi.org/10.6084/m9.figshare.25391415.v1Test |
| حقوق: |
CC BY 4.0 |
| رقم الانضمام: |
edsbas.70DA4D7 |
| قاعدة البيانات: |
BASE |
