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

“Istradefylline was negative in 4 Ames assays for bacterial mutagenicity, the chromosomal aberration assay in Chinese hamster lung cells, the micronucleus assay in mice or the UDS assay in rats.”

“In lifetime oral carcinogenicity studies, there was no evidence of carcinogenicity in mouse (0, 25, 125, or 250 mg/kg) or rat (0, 30, 100, or 320 mg/kg).”

“oral administration of istradefylline during pregnancy resulted in teratogenicity (increased incidences of fetal structural abnormalities, embryofetal and offspring mortality and growth deficits) at clinically relevant exposures and in the absence of maternal toxicity.”

“In a later study, telemeterized dogs were treated for 6 weeks at 1000 mg/kg p.o. daily and no significant effects were reported on the QT interval or respiratory parameters. The in vitro hERG assay showed no inhibition of the Ikr current at concentrations up to 2 µmol/L.”