Tolvaptan Phase 3 Efficacy and Safety Study in ADPKD

Brief Summary

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”

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

  • 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
  • Study Primary Completion Date: January 2012

Detailed Clinical Trial 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.

Interventions Used in this Clinical Trial

  • 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.
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: Tolvaptan
  • Placebo Comparator: Placebo

Outcome Measures for this Clinical Trial

Primary Measures

  • Rate of total kidney volume change(%)
    • Time Frame: 36 months
      Safety Issue?: No

Secondary Measures

  • Time to onset of multiple ADPKD outcomes
    • Time Frame: 36 months
      Safety Issue?: No
  • Evaluate long-term efficacy of tolvaptan in ADPKD using single clinical 4-markers of ADPKD progression
    • Time Frame: 36 months
      Safety Issue?: No
  • Evaluate long-term safety of tolvaptan through standard clinical measures.
    • Time Frame: 36 months
      Safety Issue?: Yes
  • Evaluate pharmacokinetic (PK), pharmacodynamic (PD) and exploratory parameters for tolvaptan in ADPKD.
    • Time Frame: 36 months
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 50 Years

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • Otsuka Pharmaceutical Development & Commercialization, Inc.
  • Collaborator
    • Otsuka Pharmaceutical Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Vicente Torres, MD, PhD, Principal Investigator, Mayo Medical Center
    • Frank Czerwiec, MD, PhD, Study Director, Otsuka Pharmaceutical Development and Commercialization, Inc.
    • Osamu Sato, Study Director, Otsuka Pharmaceutical Corporation, Ltd. Japan


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.


Clinical Trials content is provided directly by the US National Institutes of Health via and is not reviewed separately by Every page of information about a specific clinical trial contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

The URL of this page is: