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

“Nerandomilast was negative for mutagenic and clastogenic potential in a complete battery of genotoxicity assays (e.g., in vitro Ames assay, in vitro chromosome aberration assay, and an in vivo mammalian micronucleus assay).”

“Nerandomilast showed no evidence of carcinogenic potential when administered for 26 weeks to transgenic mice (Tg.rasH2) or for 104 weeks to rats up to dose levels of 60 (male)/ 100 (female) and 2 mg/kg/day, respectively.”

“Embryofoetal lethality in the form of prenatal embryo-foetal loss (post-implantation loss due to early resorptions) was observed in rats at 6 mg/kg/day (5-fold human AUC exposure at the MRHD) but was not observed in rats at 3 mg/kg/day (3-fold human AUC exposure at the MRHD) or in rabbits at 15 mg/kg/day (4-fold human AUC, unbound exposure at the MRHD).”

“No relevant adverse findings were associated with nerandomilast administration in the additional GLP core battery safety pharmacology assessments. A dose-dependent chronotropic effect on heart rate was observed in minipigs but was not considered clinically relevant.”