Tolvaptan Open-label Pilot Efficacy, Tolerability, and Safety Study in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

NCT ID: NCT00413777

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2010-06-30

Brief 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 autosomal dominant polycystic kidney disease (ADPKD).

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 anti-hypertensive 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 vasopressin V2 receptor 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.

Conditions

Polycystic Kidney, Autosomal Dominant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tolvaptan 45/15 mg/day orally for up to 4 years

Participants received tolvaptan 45 mg orally in the morning and 15 mg orally 8 hours later for up to 4 years.

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

Participants were titrated to either the tolvaptan 45/15 or 60/30 mg split-dose over a 2-month Titration Period. They received the titrated dose for 34 months during the Fixed-dose Period. Following a planned off-treatment period, participants had the option to enter an Extension Period for an additional 12 months. Tolvaptan was supplied as tablets.

Tolvaptan 60/30 mg/day orally for up to 4 years

Participants received tolvaptan 60 mg orally in the morning and 30 mg orally 8 hours later for up to 4 years.

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

Participants were titrated to either the tolvaptan 45/15 or 60/30 mg split-dose over a 2-month Titration Period. They received the titrated dose for 34 months during the Fixed-dose Period. Following a planned off-treatment period, participants had the option to enter an Extension Period for an additional 12 months. Tolvaptan was supplied as tablets.

Interventions

Tolvaptan

Participants were titrated to either the tolvaptan 45/15 or 60/30 mg split-dose over a 2-month Titration Period. They received the titrated dose for 34 months during the Fixed-dose Period. Following a planned off-treatment period, participants had the option to enter an Extension Period for an additional 12 months. Tolvaptan was supplied as tablets.

Intervention Type: DRUG

Other Intervention Names

OPC-41061

Eligibility 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 glomerular filtration rate (GFR) below 30 mL/min or who anticipate renal-replacement therapy within one year of study entry.
• Patients having contraindications to magnetic resonance imaging (MRI) or gadolinium contrast will be eligible but will not be able to participate in MRI.
• Patients taking a diuretic within 1 week of enrollment or likely to need diuretic therapy prior to Month 2.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Otsuka Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vicente Torres, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Mayo Medical Center

Frank Czerweic, MD

Role: STUDY_DIRECTOR

Otsuka Pharmaceutical Development & Commercialization, Inc.

Locations

University of Colorado

Denver, Colorado, United States

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Emory University School of Medicine

Atlanta, Georgia, United States

Univerisity of Kansas Medical Center

Kansas City, Kansas, United States

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Davita Clinical Research

Minneapolis, Minnesota, United States

Mayo Medical Center

Rochester, Minnesota, United States

Rogosin Institute

New York, New York, United States

Northwest Renal Clinic

Portland, Oregon, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Nephrology Clinical Research Center at the University of Virginia

Charlottesville, Virginia, United States

Countries

United States

References

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. doi: 10.1038/nm935. Epub 2003 Sep 21.

Reference Type: BACKGROUND

PMID: 14502283 (View on PubMed)

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. doi: 10.1038/nm1004. Epub 2004 Feb 29.

Reference Type: BACKGROUND

PMID: 14991049 (View on PubMed)

Higashihara E, Torres VE, Chapman AB, Grantham JJ, Bae K, Watnick TJ, Horie S, Nutahara K, Ouyang J, Krasa HB, Czerwiec FS; TEMPOFormula and 156-05-002 Study Investigators. Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience. Clin J Am Soc Nephrol. 2011 Oct;6(10):2499-507. doi: 10.2215/CJN.03530411. Epub 2011 Sep 8.

Reference Type: RESULT

PMID: 21903984 (View on PubMed)

St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

Reference Type: DERIVED

PMID: 39356039 (View on PubMed)

Lioudis M, Zhou X, Davenport E, Nunna S, Krasa HB, Oberdhan D, Fernandes AW. Effects of tolvaptan discontinuation in patients with autosomal dominant polycystic kidney disease: a post hoc pooled analysis. BMC Nephrol. 2023 Jun 22;24(1):182. doi: 10.1186/s12882-023-03247-6.

Reference Type: DERIVED

PMID: 37349694 (View on PubMed)

Chebib FT, Zhou X, Garbinsky D, Davenport E, Nunna S, Oberdhan D, Fernandes A. Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies. Kidney Med. 2023 Apr 14;5(6):100639. doi: 10.1016/j.xkme.2023.100639. eCollection 2023 Jun.

Reference Type: DERIVED

PMID: 37250503 (View on PubMed)

Other Identifiers

156-04-250

Identifier Type: -

Identifier Source: org_study_id