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Tolvaptan Open-Label Pilot Efficacy, Tolerability and Safety Study in ADPKD (TEMPO 2/4)

This study has been completed.
Sponsor:
Collaborator:
Otsuka Pharmaceutical Co., Ltd.
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT00413777
First received: December 18, 2006
Last updated: May 30, 2012
Last verified: May 2012
History of Changes
  Purpose

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.


Condition Intervention Phase
Polycystic Kidney, Autosomal Dominant
 Drug: tolvaptan
 Phase 2

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

Resource links provided by NLM:

Drug Information available for: Tolvaptan
U.S. FDA Resources

Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Long-term Safety [ Time Frame: 4 Years ] [ Designated as safety issue: Yes ]
    Adverse events by assigned intervention


Secondary Outcome Measures:
  • Trough Urine Osmolality at steady state [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
    Change from baseline at each study visit.

  • Change in Total Kidney Volume (TKV) [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
  • Renal function by estimated GFR [ Time Frame: 36 Months ] [ Designated as safety issue: No ]
  • Trough Urine Osmolality at Steady State [ Time Frame: Extension Day 1, Extension Year 1 ] [ Designated as safety issue: No ]
  • Change in Total Kidney Volume [ Time Frame: Extension Day 1, Extension Year 1 ] [ Designated as safety issue: No ]
  • Renal function by estimated GFR [ Time Frame: Extension Day 1, Extension Year 1 ] [ Designated as safety issue: No ]

Enrollment: 46
Study Start Date: December 2005
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fixed Low Dose Drug: tolvaptan
45 mg tablet in the morning, 15 mg tablet 8 hours later for up to 4 years
Other Name: OPC-41061
Experimental: Fixed High Dose Drug: tolvaptan
60 mg tablet in the morning, 30 mg tablet 8 hours later for up to 4 years
Other Name: OPC-41061
Experimental: Titration Drug: 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.
Other Name: OPC-41061

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413777

Locations
United States, Colorado
University of Colorado
Denver, Colorado, United States
United States, Florida
Jacksonville Center for Clinical Research
Jacksonville, Florida, United States
United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States
United States, Kansas
Univerisity of Kansas Medical Center
Kansas City, Kansas, United States
United States, Maryland
Johns Hopkins School of Medicine
Baltimore, Maryland, United States
United States, Minnesota
Davita Clinical Research
Minneapolis, Minnesota, United States
Mayo Medical Center
Rochester, Minnesota, United States
United States, New York
Rogosin Institute
New York, New York, United States
United States, Oregon
Northwest Renal Clinic
Portland, Oregon, United States
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States
United States, Virginia
Nephrology Clinical Research Center at the University of Virginia
Charlottesville, Virginia, United States
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka Pharmaceutical Co., Ltd.
Investigators
Principal Investigator: Vicente Torres, MD, PhD Mayo Medical Center
Study Director: Frank Czerweic, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT00413777     History of Changes
Other Study ID Numbers: 156-04-250
Study First Received: December 18, 2006
Last Updated: May 30, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Kidney Diseases, Cystic
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on June 17, 2013