Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD - Full Text View

Purpose

This study's purpose is to evaluate the long-term safety and efficacy of tolvaptan versus placebo in patients with ADPKD.

Condition	Intervention	Phase
Polycystic Kidney Disease, Autosomal Dominant	Drug: tolvaptan Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 3, Multi-center, Double-blind, Placebo-controlled, Parallel-arm Trial to Determine Long-term Safety and Efficacy of Oral Tolvaptan Tablets Regimens in Adult Subjects With Autosomal Dominant Polycystic Kidney Disease

Resource links provided by NLM:

Genetics Home Reference related topics: polycystic kidney disease

Drug Information available for: Tolvaptan

U.S. FDA Resources

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

Primary Outcome Measures:

Rate of total kidney volume change(%) [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to onset of multiple ADPKD outcomes [ Time Frame: 36 months ] [ Designated as safety issue: No ]
ADPKD outcomes include new onset hypertension, worsening hypertension, renal pain, worsening albuminuria and worsening renal function
Evaluate long-term efficacy of tolvaptan in ADPKD using single clinical 4-markers of ADPKD progression [ Time Frame: 36 months ] [ Designated as safety issue: No ]
Evaluate long-term safety of tolvaptan through standard clinical measures. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
Evaluate pharmacokinetic (PK), pharmacodynamic (PD) and exploratory parameters for tolvaptan in ADPKD. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Enrollment:	1445
Study Start Date:	January 2007
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Tolvaptan	Drug: tolvaptan oral tablet split-dose regimens (45/15mg, 60/30 mg or 90/30 mg) by mouth twice a day on awakening and approximately 9 hours later for 36 months. Daily dose regimen based on maximally tolerated dose. Other Name: OPC-41061 or OPC-156
Placebo Comparator: Placebo	Drug: Placebo oral tablet split-dose regimens (45/15mg Placebo, 60/30 mg Placebo or 90/30 mg Placebo) by mouth twice a day on awakening and approximately 9 hours later for 36 months. Daily dose regimen based on maximally tolerated dose.

Detailed Description:

The current study will evaluate whether tolvaptan will be potentially beneficial, while maintaining an adequate safety profile, by reducing the rate of total renal volume increase, while impacting the onset, severity and progression of other important consequences of ADPKD.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

GFR estimated at ≥60 mL/ min
Diagnosis of ADPKD and rapidly progressive kidney growth (total volume ≥750 cc) by Magnetic Resonance Imaging (MRI) at randomization
Legal adult age and able to give Informed Consent
Willingness to comply with reproductive precautions if female

Exclusion Criteria:

Prior exposure to tolvaptan or other experimental PKD therapies
Currently taking medication for purpose of affecting PKD cysts
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 or confound study objectives
Patients who are unlikely to adequately comply with study procedures
Patients having contraindications to MRI
Patients taking medications or having any illnesses likely to affect ADPKD outcomes.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00428948

Show 133 Study Locations

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 Czerwiec, MD, PhD	Otsuka Pharmaceutical Development and Commercialization, Inc.
Study Director:	Osamu Sato	Otsuka Pharmaceutical Corporation, Ltd. Japan

More Information

Publications:

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.

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.

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

Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, Perrone RD, Krasa HB, Ouyang J, Czerwiec FS; TEMPO 3:4 Trial Investigators. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012 Dec 20;367(25):2407-18. doi: 10.1056/NEJMoa1205511. Epub 2012 Nov 3.

Responsible Party:	Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:	NCT00428948 History of Changes
Other Study ID Numbers:	156-04-251, 2006-002768-24
Study First Received:	January 26, 2007
Last Updated:	February 1, 2013
Health Authority:	United States: Food and Drug Administration Canada: Health Canada Argentina: Ministry of Health Australia: Human Research Ethics Committee United Kingdom: Medicines and Healthcare Products Regulatory Agency France: National Consultative Ethics Committee for Health and Life Sciences Germany: Federal Institute for Drugs and Medical Devices Italy: Ethics Committee Belgium: Ethics Committee Netherlands: Independent Ethics Committee Poland: Ethics Committee Romania: Ethics Committee Russia: Ethics Committee Japan: Ministry of Health, Labor and Welfare Denmark: National Board of Health

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

ADPKD
Polycystic
kidney
ADPKD (Autosomal Dominant Polycystic Kidney Disease)

Additional relevant MeSH terms:

Kidney Diseases
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Kidney Diseases, Cystic

ClinicalTrials.gov processed this record on May 23, 2013

Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD (TEMPO3/4)