Study to Evaluate the Long-term Efficacy and Safety of Oral Tolvaptan Tablet Regimens in Subjects With Autosomal Dominant Polycystic Kidney Disease

Location:

Rochester, MN.

Trial status:

Open for Enrollment

Why is this study being done?

To demonstrate whether tolvaptan modifies ADPKD progression as measured by changes from baseline (from trial 156-04-251) in total kidney volume (TKV) and renal function.

Who is eligible to participate?

Inclusion Criteria:

         -  Successful completion (protocol defined completer without early termination) of a Phase 1, 2, or 3 tolvaptan ADPKD or renal impairment trial, with a confirmed diagnosis of ADPKD.

         -  Estimated GFR ≥ 30 mL/min/1.73 meter squared within 30 days prior to enrollment (calculated using the IDMS-traceable modification of diet in renal disease [4 parameter MDRD] equation with correction for gender and race). Subjects with lower estimated GFR (eGFR) may be permitted with documented medical monitor approval prior to enrollment.

       Exclusion Criteria:

         -  Inability to provide written informed consent.

         -  Men or women who will not adhere to the reproductive precautions as outlined in the Informed Consent form.

         -  Positive urine pregnancy test (women only).

         -  Subjects who are pregnant or breast-feeding.

         -  Inability to take oral medications.

         -  Subjects who have clinically significant allergic reactions to tolvaptan or chemically related structures such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate or mirtazapine)

         -  Subjects having disorders in thirst recognition or inability to access fluids.

         -  Subjects with critical electrolyte imbalances, as determined by the investigator.

         -  Subjects with or at risk of significant hypovolemia, as determined by investigator.

         -  Subjects with clinically significant anemia, as determined by investigator.

         -  Subjects with a history of substance abuse (within the last 3 years).

         -  Subjects taking other experimental (ie, non-marketed) therapies or current participation in another clinical drug or device trial. Current participation in the off-drug follow-up period of another ADPKD trial with tolvaptan is permitted.

         -  Subjects taking approved (ie, marketed) therapies, including but not limited to tolvaptan, vasopressin antagonists, anti-sense RNA therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs ( ie, octreotide, sandostatin) for the purpose of affecting PKD cysts.

       Efficacy Analysis Exclusion Criteria:

         -  Subjects having contraindications to, or interference with MRI assessments (eg, ferro-magnetic prostheses, aneurysm clips, severe claustrophobia).

         -  Subjects with a history of taking a vasopressin antagonist, outside of previous participation in a tolvaptan trial.

         -  Subjects with a history of persistent non-compliance with anti-hypertensive or other important medical therapy.

         -  Subjects taking medications or having concomitant illnesses likely to confound endpoint assessments

         -  Subjects with advanced diabetes (ie, those with poor glycemic control evidenced by a history of severely elevated hemoglobin A1C, or with evidence of advanced retinopathy, nephropathy or peripheral vascular disease due to micro-or-macro vascular disease).

Last updated:

1/1/0001

NCT ID:

NCT01214421