Tolvaptan Open-label Pilot Efficacy, Tolerability, and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

A Phase 2, Multi-center, Open-label Study to Determine Long-term Safety, Tolerability and Efficacy of Split-dose Oral Regimens of Tolvaptan Tablets in a Range of 30 to 120 mg/d in Patients With Autosomal Dominant Polycystic Kidney Disease

This study's purpose is to evaluate the long-term safety of open-label tolvaptan regimens to determine the maximally-tolerated dose and acquire pilot efficacy data in patients with autosomal dominant polycystic kidney disease (ADPKD).

Autosomal Dominant Polycystic Kidney Disease is a genetic disease classified by the formation of fluid-filled cysts in the kidneys. The accumulation of these cysts causes the kidneys to enlarge several times the normal size and leads to the eventual loss of renal function and ultimately results in renal failure in end-stage patients. This is a disease with life-threatening implications to those who have it, and their family members who may also be affected. Aside from early anti-hypertensive control and dietary protein restriction, which are presumed to offer a modest degree of protection, most surviving patients require renal replacement therapy (dialysis and transplant) and suffer from high morbidity and mortality.

A rationale for use of tolvaptan in these genetic disorders has been proven, in principle, through use of a variety of animal models. In these models, tolvaptan is effective in halting or reversing the progression of this renal disease.

The current study is being undertaken in order to evaluate whether tolvaptan, an oral vasopressin V2 receptor inhibitor, will maintain an adequate safety profile and show a potential clinical benefit by reducing total renal volume in the hopes of making an impact upon disease progression.

Inclusion Criteria:

• Prior participation in designated tolvaptan ADPKD studies (156-04-248, 156-04-249).
• Able to give Informed Consent.

Exclusion Criteria:

• Women who are breast feeding and females of childbearing potential who are not using acceptable contraceptive methods.
• In the opinion of the study investigator or sponsor may present a safety risk.
• Patients who are unlikely to adequately comply with study procedures.
• Patients who at Day 1 have an estimated glomerular filtration rate (GFR) below 30 mL/min or who anticipate renal-replacement therapy within one year of study entry.
• Patients having contraindications to magnetic resonance imaging (MRI) or gadolinium contrast will be eligible but will not be able to participate in MRI.
• Patients taking a diuretic within 1 week of enrollment or likely to need diuretic therapy prior to Month 2.