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

“A standard battery of GLP genetic toxicology studies including an in vitro bacterial reverse mutation (Ames) assay, an in vitro chromosomal aberration test in CHO cells, and an in vivo rat bone marrow micronucleus assay were completed with sotagliflozin. Sotagliflozin was neither mutagenic nor clastogenic in the three valid assays.”

“Sotagliflozin did not cause any treatment-related, statistically significant neoplasms in transgenic RasH2 (Tg.RasH2) mice or the rat in either sex.”

“Sotagliflozin was not teratogenic in the rat at 100 mg/kg (40X MHRD) or in the rabbit at 200 mg/kg (9X MHRD). In rats, a higher dose (350 mg/kg; 161X MHRD) caused both maternal and fetal toxicity including significant reduction in maternal weight gain, embryo-lethality, reduced fetal weights, altered sex ratio, and cardiovascular and skeletal malformations.”

“Sotagliflozin has an IC50 >23.5 µM in the human ether-a-go-go related gene (hERG) assay. A cardiac telemetry study in Beagle dogs showed that sotagliflozin had no significant effect on QT or QTc interval (corrected with the Fridericia method) at dose levels up to 500 mg/kg.”

“A standard battery of GLP genetic toxicology studies including an in vitro bacterial reverse mutation (Ames) assay, an in vitro chromosomal aberration test in CHO cells, and an in vivo rat bone marrow micronucleus assay were completed with sotagliflozin. Sotagliflozin was neither mutagenic nor clastogenic in the three valid assays.”

“A standard battery of GLP genetic toxicology studies including an in vitro bacterial reverse mutation (Ames) assay, an in vitro chromosomal aberration test in CHO cells, and an in vivo rat bone marrow micronucleus assay were completed with sotagliflozin. Sotagliflozin was neither mutagenic nor clastogenic in the three valid assays.”

“A standard battery of GLP genetic toxicology studies including an in vitro bacterial reverse mutation (Ames) assay, an in vitro chromosomal aberration test in CHO cells, and an in vivo rat bone marrow micronucleus assay were completed with sotagliflozin. Sotagliflozin was neither mutagenic nor clastogenic in the three valid assays.”

“The carcinogenic potential of sotagliflozin was evaluated in a 26-week transgenic RasH2 mouse carcinogenicity study and a 2-year rat carcinogenicity study.”

“The carcinogenic potential of sotagliflozin was evaluated in a 26-week transgenic RasH2 mouse carcinogenicity study and a 2-year rat carcinogenicity study. The Executive Carcinogenicity Committee (ECAC) concluded that both studies adequately addressed the carcinogenicity of sotagliflozin”

“Sotagliflozin has an IC50 >23.5 µM in the human ether-a-go-go related gene (hERG) assay. A cardiac telemetry study in Beagle dogs showed that sotagliflozin had no significant effect on QT or QTc interval (corrected with the Fridericia method) at dose levels up to 500 mg/kg.”