Osilodrostat and pasireotide monotherapies can significantly affect in the histology and mean weights of the pituitary and adrenal glands, liver, and ovary/oviduct. Osilodrostat is associated with adrenocortical hypertrophy and hepatocellular hypertrophy. The combination of Osilodrostat with pasireotide ameliorates the liver and adrenal gland changes observed with monotherapy and does not exacerbate any target organ changes. Cmax and AUC(0–24h) of Osilodrostat and pasireotide increase in an approximately dose-proportional manner. Osilodrostat treatment reduces urinary free cortisol in patients with Cushing's disease; 78.9% has normal urinary free cortisol at week 22.

Sixty male and 60 female rats are randomized into single-sex groups to receive daily doses of pasireotide (0.3 mg/kg/day, s.c.), osilodrostat (20 mg/kg/day, p.o.), osilodrostat/pasireotide in combination (low dose, 1.5/0.03 mg/kg/day; mid-dose, 5/0.1 mg/kg/day; or high dose, 20/0.3 mg/kg/day), or vehicle for 13 weeks.

928134-65-0

C13H10FN3

227.242

LCI699

DMSO:83.3 mg/mL
Powder: -20°C for 3 years
In solvent: -80°C for 2 years