Truqap: genotox, carcinogenicity and repro: done or skipped?

“Capivasertib induced a statistically significant increase in the incidence of micronucleated immature erythrocytes at 150 mg/kg in the in vivo rat bone marrow micronucleus assay through an aneugenic mode of action.”

“Carcinogenicity studies with capivasertib were not warranted to support this NDA, as the proposed indication is for advanced cancer.”

“Administration of capivasertib to rats prior to implantation until Day 16 of gestation resulted in minor fetal visceral variations, an increase in post-implantation loss, and reduced gravid uterine and fetal weights at 150 mg/kg/day.”

“In safety pharmacology studies, single oral administration of capivasertib at 5, 30 and 40 mg/kg induced decreased heart rate for up to 8 hours, peak decreases in systolic and diastolic blood pressure with recovery within 4 hours, sustained prolongation of QTcR and increases in LVdP/dt+ along with elevation of both glucose and insulin levels in dogs.”