Stage of Development

Lixivaptan has undergone extensive pre-clinical in-vitro and in-vivo studies, as well as extensive Phase II human studies. It has been found to be safe and well tolerated when administered to normal healthy subjects at single doses and as multiple total daily doses.

Phase II Findings

In normal healthy subjects, oral doses of Lixivaptan appeared to be rapidly absorbed, with dose-related increases in Cmax and AUC. VPA-985 produced dose-related increases in urine flow (Uflow) and free water clearance (CH2O), with prolongation of effect at higher doses and corresponding increases in serum sodium and serum osmolality (Sosm), and decreases in urine osmolality (Uosm).

In patients with heart failure, Cirrhosis or SIADH, Lixivaptan was also well tolerated. Lixivaptan produced increased Uflow and CH2O, and decreased Uosm in these patient populations when administered as a single dose. Multiple doses were well tolerated and produced pharmacodynamic effects similar to those of single doses.

Lixivaptan was also well tolerated when given in combination with therapeutic doses of furosemide, HCTZ, digoxin, warfarin, enalapril and spironolactone, and produced increases in U0 and serum sodium as expected.