Long Term Safety of Immediate-release Tolvaptan in Subjects With Autosomal Dominant Polycystic Kidney Disease

NCT ID: NCT02251275

Last Updated: 2019-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1803 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-10-17
• Study Completion Date: 2018-11-09

Brief Summary

The purpose of the trial was to evaluate and describe the long term safety of tolvaptan in participants with autosomal dominant polycystic kidney disease (ADPKD).

Detailed Description

This was a Phase 3b trial to evaluate and describe the long term safety of tolvaptan treatment in ADPKD participants with chronic kidney disease (CKD). Eligible participants could enroll into Trial 156-13-211 after completing the follow-up visit(s) of their previous trial (156-13-210, 156-08-271, 156-04-251, or 156-09-290). Renal function was assessed during screening by using historical laboratory values for serum creatinine levels to calculate the estimated glomerular filtration rate (eGFR).

Conditions

Polycystic Kidney, Autosomal Dominant

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tolvaptan

Tolvaptan was self-administered orally as split-dose regimens. The dose regimens used in this trial were 15/15 milligram (mg), 30/15 mg, 45/15 mg, 60/30 mg, or 90/30 mg. Starting doses were dependent upon the participant's previous trial as follows:

• Trial 156-13-210: initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.
• Trial 156-08-271: retained the last dose level of tolvaptan received in the trial (45/15 mg, 60/30 mg, or 90/30 mg) and started at that same dose in Trial 156-13-211.
• Other Trials (156-04-251 and 156-09-290): initiated on tolvaptan at a split-dose of 45/15 mg with upward titration every 3 to 4 days to 60/30 mg or 90/30 mg per day according to tolerability.

Group Type: EXPERIMENTAL

Tolvaptan

Intervention Type: DRUG

Tolvaptan tablets (15 or 30 mg) self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later

Interventions

Tolvaptan

Tolvaptan tablets (15 or 30 mg) self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later

Intervention Type: DRUG

Other Intervention Names

OPC-41061

Eligibility Criteria

Inclusion Criteria

• Male and female participants ≥ 18 years with confirmed diagnosis of ADPKD (during participation in prior tolvaptan trials) who have completed and transferred from the double-blind Trial 156-13-210 (12-month period including post treatment follow-up, regardless of whether this was on-treatment or off-treatment), or completed Trial 156-08-271 or a prior tolvaptan trial, or interrupted or discontinued treatment in a prior tolvaptan ADPKD trial other than Trial 156-13-210. Participants may be enrolled with the medical monitor approval, and additional close monitoring may be required at the beginning of the trial.
• eGFR ≥ 20 milliliter (mL)/minute (min)/1.73 meter squared (m^2) within 3 months prior to the baseline visit. Participants who have an eGFR ≤ 20 mL/min/1.73 m^2 may be enrolled with medical monitor approval.

Exclusion Criteria

• Need for chronic diuretic use
• Hepatic impairment based on liver function abnormalities other than that expected for ADPKD with cystic liver disease
• Women of childbearing potential who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of investigational medicinal product (IMP)
• Women who are breast-feeding and/or who have a positive pregnancy test result prior to receiving IMP.
• Participants with contraindications to required trial assessments (contraindications to optional assessments, for example, magnetic resonance imaging [MRI] are not a limitation).
• Participants who in the opinion of the investigator or the medical monitor, have a medical history or medical finding inconsistent with safety or trial compliance

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

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Birmingham, Alabama, United States

Huntsville, Alabama, United States

Mobile, Alabama, United States

Phoenix, Arizona, United States

Tempe, Arizona, United States

Tucson, Arizona, United States

La Jolla, California, United States

Los Angeles, California, United States

Los Angeles, California, United States

San Francisco, California, United States

Stanford, California, United States

Aurora, Colorado, United States

Denver, Colorado, United States

Denver, Colorado, United States

New Haven, Connecticut, United States

Hudson, Florida, United States

Jacksonville, Florida, United States

Miami, Florida, United States

Ocala, Florida, United States

Port Charlotte, Florida, United States

Tampa, Florida, United States

Atlanta, Georgia, United States

Augusta, Georgia, United States

Meridian, Idaho, United States

Chicago, Illinois, United States

Chicago, Illinois, United States

Kansas City, Kansas, United States

Wichita, Kansas, United States

Baton Rouge, Louisiana, United States

Baltimore, Maryland, United States

Baltimore, Maryland, United States

Greenbelt, Maryland, United States

Rockville, Maryland, United States

Boston, Massachusetts, United States

Springfield, Massachusetts, United States

Detroit, Michigan, United States

Grand Rapids, Michigan, United States

Kalamazoo, Michigan, United States

Pontiac, Michigan, United States

Roseville, Michigan, United States

Rochester, Minnesota, United States

St Louis, Missouri, United States

Las Vegas, Nevada, United States

Reno, Nevada, United States

Eatontown, New Jersey, United States

Voorhees Township, New Jersey, United States

Buffalo, New York, United States

Laurelton, New York, United States

Mineola, New York, United States

New York, New York, United States

New York, New York, United States

Asheville, North Carolina, United States

Chapel Hill, North Carolina, United States

Charlotte, North Carolina, United States

Winston-Salem, North Carolina, United States

Fargo, North Dakota, United States

Akron, Ohio, United States

Cincinnati, Ohio, United States

Cincinnati, Ohio, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Portland, Oregon, United States

Bethlehem, Pennsylvania, United States

Doylestown, Pennsylvania, United States

Philadelphia, Pennsylvania, United States

Charleston, South Carolina, United States

Columbia, South Carolina, United States

Orangeburg, South Carolina, United States

Knoxville, Tennessee, United States

Nashville, Tennessee, United States

Nashville, Tennessee, United States

Arlington, Texas, United States

Houston, Texas, United States

Houston, Texas, United States

McAllen, Texas, United States

Burlington, Vermont, United States

Arlington, Virginia, United States

Charlottesville, Virginia, United States

Norfolk, Virginia, United States

Wenatchee, Washington, United States

Morgantown, West Virginia, United States

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina

Junín, Buenos Aires, Argentina

Pergamino, Buenos Aires, Argentina

Pilar, Buenos Aires, Argentina

Córdoba, , Argentina

Córdoba, , Argentina

Córdoba, , Argentina

Camperdown, New South Wales, Australia

New Lambton Heights, New South Wales, Australia

St Leonards, New South Wales, Australia

Westmead, New South Wales, Australia

Woolloongabba, Queensland, Australia

Adelaide, South Australia, Australia

Launceston, Tasmania, Australia

Parkville, Victoria, Australia

Reservoir, Victoria, Australia

Richmond, Victoria, Australia

Perth, Western Australia, Australia

Aalst, , Belgium

Brussels, , Belgium

Brussels, , Belgium

Edegem, , Belgium

Ghent, , Belgium

Kortrijk, , Belgium

Leuven, , Belgium

Liège, , Belgium

Edmonton, Alberta, Canada

Mount Pearl, Newfoundland and Labrador, Canada

Scarborough Village, Ontario, Canada

Toronto, Ontario, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Brno, , Czechia

České Budějovice, , Czechia

Hradec Králové, , Czechia

Jihlava, , Czechia

Jilemnice, , Czechia

Liberec, , Czechia

Ostrava, , Czechia

Prague, , Czechia

Prague, , Czechia

Aalborg, , Denmark

Aarhus N, , Denmark

Holstebro, , Denmark

Heidelberg, Baden-Wurttemberg, Germany

Munich, Bavaria, Germany

Nuremberg, Bavaria, Germany

Wiesbaden, Hesse, Germany

Düsseldorf, North Rhine-Westphalia, Germany

Essen, North Rhine-Westphalia, Germany

Dresden, Saxony, Germany

Berlin, , Germany

Budapest, , Hungary

Pécs, , Hungary

Szeged, , Hungary

Ashkelon, , Israel

Jerusalem, , Israel

Nahariya, , Israel

Petah Tikva, , Israel

Ramat Gan, , Israel

Tel Aviv, , Israel

Montichiari, Brescia, Italy

Bari, , Italy

Lecco, , Italy

Milan, , Italy

Milan, , Italy

Modena, , Italy

Napoli, , Italy

Pavia, , Italy

Amsterdam, , Netherlands

Groningen, , Netherlands

Nijmegen, , Netherlands

Bergen, , Norway

Ciechanów, , Poland

Gdansk, , Poland

Golub-Dobrzyń, , Poland

Krakow, , Poland

Lodz, , Poland

Lodz, , Poland

Lublin, , Poland

Szczecin, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Bucharest, , Romania

Bucharest, , Romania

Bucharest, , Romania

Oradea, , Romania

Kemerovo, , Russia

Krasnoyarsk, , Russia

Saint Petersburg, , Russia

Saint Petersburg, , Russia

Yaroslavl, , Russia

Pretoria, Gauteng, South Africa

Durban, KwaZulu-Natal, South Africa

Cape Town, Western Cape, South Africa

Barcelona, , Spain

Ciudad Real, , Spain

Madrid, , Spain

Madrid, , Spain

Valencia, , Spain

Gothenburg, , Sweden

Linköping, , Sweden

Stockholm, , Sweden

Stockholm, , Sweden

Uppsala, , Sweden

Belfast, County Antrim, United Kingdom

Exeter, Devon, United Kingdom

Hull, East Riding Of Yorkshire, United Kingdom

Brighton, East Sussex, United Kingdom

London, Greater London, United Kingdom

London, Greater London, United Kingdom

London, Greater London, United Kingdom

Manchester, Greater Manchester, United Kingdom

Salford, Greater Manchester, United Kingdom

Stevenage, Hertfordshire, United Kingdom

Inverness, Highland Region, United Kingdom

Leicester, Leicestershire, United Kingdom

Edinburgh, Lothian Region, United Kingdom

Liverpool, Norfolk, United Kingdom

Sheffield, South Yorkshire, United Kingdom

Stoke-on-Trent, Staffordshire, United Kingdom

Newcastle upon Tyne, Tyne & Wear, United Kingdom

Coventry, Warwickshire, United Kingdom

Birmingham, West Midlands, United Kingdom

Middlesbrough, , United Kingdom

Swansea, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Canada; Czechia; Denmark; Germany; Hungary; Israel; Italy; Netherlands; Norway; Poland; Romania; Russia; South Africa; Spain; Sweden; United Kingdom

References

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)

Alpers DH, Lewis JH, Hunt CM, Freston JW, Torres VE, Li H, Wang W, Hoke ME, Roth SE, Westcott-Baker L, Estilo A. Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials. Am J Kidney Dis. 2023 Mar;81(3):281-293.e1. doi: 10.1053/j.ajkd.2022.08.012. Epub 2022 Sep 30.

Reference Type: DERIVED

PMID: 36191725 (View on PubMed)

Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Lee J, Hoke ME, Estilo A, Sergeyeva O. Multicenter Study of Long-Term Safety of Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. Clin J Am Soc Nephrol. 2020 Dec 31;16(1):48-58. doi: 10.2215/CJN.10250620. Epub 2020 Dec 29.

Reference Type: DERIVED

PMID: 33376102 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

156-13-211

Identifier Type: -

Identifier Source: org_study_id