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

“Opicapone was negative in a standard battery of genetic toxicology (Ames, in vitro chromosomal aberration in peripheral human lymphocytes, in vivo CD-1 mouse micronucleus) assays.”

“No drug-related tumors were observed in mouse or rat.”

“In the reproductive and developmental toxicology studies in rat, opicapone was tested at oral doses up to 1000 mg/kg/day, using standard study designs. No adverse effects on fertility or on embryofetal (EFD) or pre- and postnatal development (PPND) were observed.”

“BIA 9-1067 had no relevant effects on hERG-mediated currents in HEK cells or on action potential of isolated Purkinje fibers. In vivo administration in rat and monkey resulted in no test-article effects on electrocardiograms, respiratory function, or behavior.”

“BIA 9-1067 and metabolite BIA 9-1079 were negative in genetic toxicology (Ames, in vitro chromosomal aberration in human peripheral blood lymphocytes, and in vivo mouse micronucleus) studies.”

“BIA 9-1067 and metabolite BIA 9-1079 were negative in genetic toxicology (Ames, in vitro chromosomal aberration in human peripheral blood lymphocytes, and in vivo mouse micronucleus) studies.”

“BIA 9-1067 and metabolite BIA 9-1079 were negative in genetic toxicology (Ames, in vitro chromosomal aberration in human peripheral blood lymphocytes, and in vivo mouse micronucleus) studies.”

“Sufficient numbers of animals survived through 104 weeks in both studies, and there were no drug-related neoplasms in either study. Under the conditions of these studies, BIA 9-1067 was found to be non-carcinogenic.”

“Two long term carcinogenicity studies have been completed with Opicapone. Mice were dosed with oral opicapone at 100, 500/375 and 1000/500 mg/kg/day and rats were dosed with 100, 500 and 1000 mg/kg/day).”

“At concentrations up to 10 µM BIA 9-1067 had no relevant effects on hERG-mediated currents in HEK cells or on action potential of isolated Purkinje fibers.”