[3] Cyst growth displaces and destroys normal kidney tissue, leading to a decreased number and function of nephrons.

Treatment with specific V2 receptor antagonists have shown a reduction in kidney size and cyst volume in animal models of PKD.

[4][5] In particular, lixivaptan has demonstrated beneficial effects on cystic disease progression in rat and mouse models of ADPKD.

The FDA-approved prescribing information for tolvaptan for ADPKD includes a boxed warning for the risk of serious liver toxicity.

[11] Lixivaptan was previously administered to more than 1600 subjects across 36 clinical studies as part of a prior clinical development program for the treatment of hyponatremia sponsored by Cardiokine, Inc.[1] Across these studies, lixivaptan showed prolonged inhibition of the vasopressin V2 receptor, as measured by changes in pharmacodynamic markers such as urine osmolality, plasma copeptin, and estimated glomerular filtration rate (eGFR).

If the ACTION study is successful, it will provide the main clinical evidence supporting the potential safety and efficacy of lixivaptan for the treatment of ADPKD.

This part of the trial will compare the change in estimated glomerular filtration rate (eGFR) measurements between the two groups to investigate the efficacy of lixivaptan in slowing the decline in kidney function.

At the completion of the 52 weeks maintenance period, patients will be eligible to continue to receive lixivaptan in an open label extension study.