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

NCT00413777 | Completed Phase 2 Results

• 1 other identifier: 156-04-250
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 11

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).

Conditions

Polycystic Kidney, Autosomal Dominant

Outcome Measures

Primary Outcomes (1)

• Safety Assessments Based on Vital Signs, Electrocardiogram (ECG's), Clinical Laboratory Tests, Physical Examinations Are Reported as Adverse Events (AEs) Upon Study Physician Discretion.

  An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in a study , whether or not it was considered drug-related by the study physician. A treatment-emergent AE (TEAE) was defined as an AE that started after start of study drug treatment; or if the event was continuous from Baseline and was serious, study drug related, or resulted in death, discontinuation.

  AEs were recorded from screening (ICF was signed) until 7-Day follow-up

Secondary Outcomes (20)

• Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to First Daily Dose.

  Baseline to Month 36

• Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Second Daily Dose.

  Baseline to Month 24

• Mean Change From Baseline in Trough Urine Osmolality at Steady State Prior to Bedtime.

  Baseline to Month 24

• Percent Change From Baseline in Renal Volume.

  Baseline to Month 36

• Change From Pre-dose Baseline in Renal Function Estimated by Glomerular Filtration Rate (GFR).

  Baseline to Month 36

Study Arms (2)

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

EXPERIMENTAL

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

Drug: Tolvaptan

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

EXPERIMENTAL

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

Drug: Tolvaptan

Interventions

Tolvaptan 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.

Also known as: OPC-41061

Tolvaptan 45/15 mg/day orally for up to 4 years; Tolvaptan 60/30 mg/day orally for up to 4 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior participation in designated tolvaptan ADPKD studies (156-04-248, 156-04-249).
• Able to give Informed Consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator

Study Sites (11)

University of Colorado

Denver, Colorado, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Location

Emory University School of Medicine

Atlanta, Georgia, United States

Location

Univerisity of Kansas Medical Center

Kansas City, Kansas, United States

Location

Johns Hopkins School of Medicine

Baltimore, Maryland, United States

Location

Davita Clinical Research

Minneapolis, Minnesota, United States

Location

Mayo Medical Center

Rochester, Minnesota, United States

Location

Rogosin Institute

New York, New York, United States

Location

Northwest Renal Clinic

Portland, Oregon, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Location

Nephrology Clinical Research Center at the University of Virginia

Charlottesville, Virginia, United States

Location

Related Publications (6)

• 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.

  PMID: 14502283 BACKGROUND

• 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.

  PMID: 14991049 BACKGROUND

• 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.

  PMID: 21903984 RESULT

• 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.

  PMID: 39356039 DERIVED

• 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.

  PMID: 37349694 DERIVED

• 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.

  PMID: 37250503 DERIVED

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant

Interventions

Tolvaptan

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Affairs
• Organization: Otsuka Pharmaceutical Development and Commercialization, Inc.

800 562-3974

Study Officials

• Vicente Torres, MD, PhD

  Mayo Medical Center

  PRINCIPAL INVESTIGATOR

• Frank Czerweic, MD

  Otsuka Pharmaceutical Development & Commercialization, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2006
• First Posted: December 20, 2006
• Study Start: December 1, 2005
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: July 2, 2017
• Results First Posted: July 2, 2017

Record last verified: 2017-05

Locations

US (11)