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

“Vibegron was not mutagenic in in vitro microbial reverse mutation (Ames) assays, showed no genotoxic activity in an in vitro human peripheral blood lymphocyte chromosomal aberration assay, and did not increase the frequency of micronucleated polychromatic erythrocytes in an in vivo rat bone marrow micronucleus assay.”

“Two year carcinogenicity studies were also conducted in mice and rats, with no treatment-related malignancies observed in either species at adequate exposure margins”

“No embryo-fetal developmental toxicity was observed in rats at doses up to 300 mg/kg/day (1867-fold the AUC at the clinical dose) or in rabbits at doses up to 100 mg/kg/day (285-fold the AUC at the clinical dose).”

“Cardiac safety pharmacology studies in the rhesus monkey indicated that vibegron significantly increased heart rate, respiration rate and body temperature.”

“Vibegron was not mutagenic in in vitro microbial reverse mutation (Ames) assays, showed no genotoxic activity in an in vitro human peripheral blood lymphocyte chromosomal aberration assay, and did not increase the frequency of micronucleated polychromatic erythrocytes in an in vivo rat bone marrow micronucleus assay.”

“Vibegron was not mutagenic in in vitro microbial reverse mutation (Ames) assays, showed no genotoxic activity in an in vitro human peripheral blood lymphocyte chromosomal aberration assay, and did not increase the frequency of micronucleated polychromatic erythrocytes in an in vivo rat bone marrow micronucleus assay.”

“Vibegron was not mutagenic in in vitro microbial reverse mutation (Ames) assays, showed no genotoxic activity in an in vitro human peripheral blood lymphocyte chromosomal aberration assay, and did not increase the frequency of micronucleated polychromatic erythrocytes in an in vivo rat bone marrow micronucleus assay.”

“Two year carcinogenicity studies were also conducted in mice and rats, with no treatment-related malignancies observed in either species at adequate exposure margins”

“Two year carcinogenicity studies were also conducted in mice and rats, with no treatment-related malignancies observed in either species at adequate exposure margins”

“In CHO-K1 Chinese Hamster Ovary cells, at a concentration of 31 μM (112-fold the MRHD of 75 mg using Cmax)(N=5), MK-4618 had no statistically significant effect on hERG channel tail current, but at the maximum testable concentration of 101 μM (365­ fold)(N=4), it inhibited hERG current by 21.4%.”