A comprehensive analysis of liver safety across zibotentan oncology trials: knowledge of the past offers new perspectives on the present.
Expert Opin Drug Saf
; 23(4): 477-486, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38469902
ABSTRACT
BACKGROUND:
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. RESEARCH DESIGN ANDMETHODS:
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.RESULTS:
A total of 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 seven patients receiving zibotentan who met criteria for potential Hy's Law, there were no cases of drug-induced liver injury.CONCLUSIONS:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug-Related Side Effects and Adverse Reactions
/
Chemical and Drug Induced Liver Injury
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
Expert Opin Drug Saf
/
Expert opin. drug saf. (Online)
/
Expert opinion on drug safety (Online)
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2024
Document type:
Article
Country of publication:
Reino Unido