Evacetrapib
High-dose evacetrapib causes toxicity in parent rats but leaves fertility and fetal development unharmed in rats and rabbits (Birth Defects Res 2017)
Original title: Fertility and Embryo-Fetal Development Assessment in Rats and Rabbits with Evacetrapib: A Cholesteryl Ester Transfer Protein Inhibitor
Evacetrapib was administered by oral gavage to rats before mating through necropsy or gestation day 17 (60 to 600 mg/kg) and to rabbits from gestation days 7 to 19 or from a week before mating through gestation day 19 (1 to 100 mg/kg/day), to assess fertility and embryo-fetal development. In rats, 600 mg/kg/day caused decreased body weight, food consumption, and moribund euthanasia, and 300 mg/kg/day reduced food consumption, but there were no adverse effects on estrus cycling, fertility indices, sperm parameters, maternal reproductive parameters, male reproductive tissue, or fetal viability, growth, or morphology; the only developmental finding was a nonadverse, transient increase in 14th rudimentary ribs at 600 mg/kg/day. In rabbits, only slight decreases in maternal body weight and food consumption occurred at 100 mg/kg/day, with no adverse developmental effects. Overall, no adverse effects on fertility or embryo-fetal development were observed in rats up to 600 mg/kg/day or in rabbits up to 100 mg/kg/day.
Original abstract
Background: The purpose of these studies was to evaluate the effects of evacetrapib on male and female fertility and on embryo-fetal development (EFD).
Methods: Evacetrapib, a potent and selective inhibitor of cholesteryl ester transfer protein (CETP), was administered daily by oral gavage starting 2 weeks (for female) or 4 weeks (for male) before mating, during cohabitation, and until necropsy in the male rat fertility study or through gestation day (GD) 17 in the female rat combined fertility/EFD study. For rabbit EFD studies, animals were dosed from GDs 7 to 19 or from 1 week before mating through GD 19. Dose levels of evacetrapib ranged from 60 to 600 mg/kg for rats and from 1 to 100 mg/kg/day for rabbits.
Results: Parental findings in rats included decreased body weight and food consumption and moribund euthanasia in animals given 600 mg/kg/day and decreased food consumption at 300 mg/kg/day. There were no adverse effects on estrus cycling, fertility indices, sperm parameters, maternal reproductive parameters, male reproductive tissue, or fetal viability, growth, or external/visceral morphology. An increase in the incidence of 14th rudimentary ribs, a minor, transient variation considered nonadverse, was the only significant developmental finding in rats given 600 mg/kg/day. Slight decreases in body weight and food consumption at 100 mg/kg/day were the only maternal effects observed in rabbits with no adverse developmental effects noted.
Conclusion: No adverse effects on fertility or EFD were observed in rats at doses up to 600 mg/kg/day and no adverse effects on EFD were noted in rabbits at doses up to 100 mg/kg/day. Birth Defects Research 109:513-527, 2017. © 2017 Wiley Periodicals, Inc.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.