Tolvaptan Open-Label Pilot Efficacy, Tolerability and Safety Study in ADPKD

Polycystic Kidney, Autosomal Dominant Clinical Trial

— TEMPO 2/4  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00413777
• Other study ID #: 156-04-250
• Status: Completed
• Phase: Phase 2
• First received: December 18, 2006
• Last updated: May 30, 2012
• Start date: December 2005
• Est. completion date: June 2010

Study information

• Verified date: May 2012
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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 ADPKD.

Description:

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 antihypertensive 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 AVP 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 GFR below 30 mL/min or who anticipate renal-replacement therapy within one year of study entry.

• Patients having contraindications to MRI or gadolinium contrast will be eligible but will not be able to participate in MRI

• Patients taking within 1 week of enrollment, or likely to need diuretic therapy, prior to Month 2

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• tolvaptan
45 mg tablet in the morning, 15 mg tablet 8 hours later for up to 4 years
• tolvaptan
60 mg tablet in the morning, 30 mg tablet 8 hours later for up to 4 years
• tolvaptan
30mg/15mg, 45mg/15mg, 60mg/30mg, 90mg/30mg tablets with the higher strength taken in the morning and the second dose 8 hours later. Split-dose regimens titrated weekly to maximally tolerated dose group. Maximum tolerated dose maintained up to 2 months.

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Johns Hopkins School of Medicine	Baltimore	Maryland
United States	Nephrology Clinical Research Center at the University of Virginia	Charlottesville	Virginia
United States	University of Colorado	Denver	Colorado
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Univerisity of Kansas Medical Center	Kansas City	Kansas
United States	Davita Clinical Research	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Rogosin Institute	New York	New York
United States	Northwest Renal Clinic	Portland	Oregon
United States	Mayo Medical Center	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.	Otsuka Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

United States, 

References & Publications (2)

Gattone VH 2nd, Wang X, Harris PC, Torres VE. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med. 2003 Oct;9(10):1323-6. Epub 2003 Sep 21. — View Citation

Torres VE, Wang X, Qian Q, Somlo S, Harris PC, Gattone VH 2nd. Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease. Nat Med. 2004 Apr;10(4):363-4. Epub 2004 Feb 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long-term Safety	Adverse events by assigned intervention	4 Years	Yes
Secondary	Trough Urine Osmolality at steady state	Change from baseline at each study visit.	36 Months	No
Secondary	Change in Total Kidney Volume (TKV)		36 Months	No
Secondary	Renal function by estimated GFR		36 Months	No
Secondary	Trough Urine Osmolality at Steady State		Extension Day 1, Extension Year 1	No
Secondary	Change in Total Kidney Volume		Extension Day 1, Extension Year 1	No
Secondary	Renal function by estimated GFR		Extension Day 1, Extension Year 1	No