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

November 7, 2019 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

A Phase 3b, Multi-center, Open-label Trial to Evaluate the Long Term Safety of Immediate-release Tolvaptan (OPC-41061, 30 mg to 120 mg/Day, Split Dose) in Subjects With Autosomal Dominant Polycystic Kidney Disease

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

1803

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Córdoba, Argentina, X5000JHQ
      • Córdoba, Argentina, X5016KEH
      • Córdoba, Argentina, X5166BPW
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1093AAS
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1425APQ
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1429BWN
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1431FWO
      • Junin, Buenos Aires, Argentina, 6000
      • Pergamino, Buenos Aires, Argentina, B2700CPM
      • Pilar, Buenos Aires, Argentina, B1629ODT
  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
      • New Lambton Heights, New South Wales, Australia, 2305
      • St Leonards, New South Wales, Australia, 2065
      • Westmead, New South Wales, Australia, 2145
    • Queensland
      • Woolloongabba, Queensland, Australia, 4102
    • South Australia
      • Adelaide, South Australia, Australia, 5000
    • Tasmania
      • Launceston, Tasmania, Australia, 7250
    • Victoria
      • Parkville, Victoria, Australia, 3050
      • Reservoir, Victoria, Australia, 3073
      • Richmond, Victoria, Australia, 3121
    • Western Australia
      • Perth, Western Australia, Australia, 6000
  • Belgium
      • Aalst, Belgium, 9300
      • Bruxelles, Belgium, 1200
      • Bruxelles, Belgium, 1090
      • Edegem, Belgium, 2650
      • Gent, Belgium, 9000
      • Kortrijk, Belgium, 8500
      • Leuven, Belgium, 3000
      • Liège, Belgium, 4000
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2B7
    • Newfoundland and Labrador
      • Mount Pearl, Newfoundland and Labrador, Canada, A1N 3J5
    • Ontario
      • Scarborough, Ontario, Canada, M1H 3G4
      • Toronto, Ontario, Canada, M5G 2N2
      • Toronto, Ontario, Canada, M4C 5T2
    • Quebec
      • Montreal, Quebec, Canada, H4J 1C5
  • Czechia
      • Brno, Czechia, 625 00
      • Ceske Budejovice, Czechia, 370 87
      • Hradec Kralove, Czechia, 500 05
      • Jihlava, Czechia, 586 01
      • Jilemnice, Czechia, 51401
      • Liberec, Czechia, 460 63
      • Ostrava, Czechia, 708 52
      • Praha 2, Czechia, 128 08
      • Praha 4, Czechia, 140 21
  • Denmark
      • Aalborg, Denmark, 9100
      • Aarhus N, Denmark, 8200
      • Holstebro, Denmark, 7500
  • Germany
      • Berlin, Germany, 10117
    • Baden Wuerttemberg
      • Heidelberg, Baden Wuerttemberg, Germany, 69120
    • Bayern
      • Muenchen, Bayern, Germany, 81675
      • Nuernberg, Bayern, Germany, 90471
    • Hessen
      • Wiesbaden, Hessen, Germany, 65191
    • Nordrhein Westfalen
      • Duesseldorf, Nordrhein Westfalen, Germany, 40210
      • Essen, Nordrhein Westfalen, Germany, 45147
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
  • Hungary
      • Budapest, Hungary, 1032
      • Pecs, Hungary, 7623
      • Szeged, Hungary, 6720
  • Israel
      • Ashkelon, Israel, 78278
      • Jerusalem, Israel, 9112001
      • Nahariya, Israel, 2210001
      • Petach Tikva, Israel, 491004
      • Ramat-Gan, Israel, 52621
      • Tel Aviv, Israel, 6423906
  • Italy
      • Bari, Italy, 70124
      • Lecco, Italy, 23900
      • Milano, Italy, 20122
      • Milano, Italy, 20132
      • Modena, Italy, 41124
      • Napoli, Italy, 80138
      • Pavia, Italy, 27100
    • Brescia
      • Montichiari, Brescia, Italy, 25018
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
      • Groningen, Netherlands, 9713 GZ
      • Nijmegen, Netherlands, 6525 GA
  • Norway
      • Bergen, Norway, 5021
  • Poland
      • Ciechanow, Poland, 06-400
      • Gdansk, Poland, 80-952
      • Golub Dobrzyn, Poland, 87-400
      • Krakow, Poland, 31-559
      • Lodz, Poland, 92-213
      • Lodz, Poland, 93-347
      • Lublin, Poland, 20-954
      • Szczecin, Poland, 70-111
      • Warszawa, Poland, 04-749
      • Wroclaw, Poland, 50-556
  • Romania
      • Bucuresti, Romania, 011794
      • Bucuresti, Romania, 022328
      • Bucuresti, Romania, 010731
      • Oradea, Romania, 410469
  • Russian Federation
      • Kemerovo, Russian Federation, 650002
      • Krasnoyarsk, Russian Federation, 660062
      • Saint-Petersburg, Russian Federation, 197022
      • Saint-Petersburg, Russian Federation, 19401344
      • Yaroslavl, Russian Federation, 150062
  • South Africa
    • Gauteng
      • Pretoria, Gauteng, South Africa, 0002
    • KwaZulu-Natal
      • Durban, KwaZulu-Natal, South Africa, 4001
    • Western Cape
      • Cape Town, Western Cape, South Africa, 7925
  • Spain
      • Barcelona, Spain, 08907
      • Ciudad Real, Spain, 13005
      • Madrid, Spain, 28046
      • Madrid, Spain, 28041
      • Valencia, Spain, 46017
  • Sweden
      • Göteborg, Sweden, 413 45
      • Linköping, Sweden, 58185
      • Stockholm, Sweden, 17176
      • Stockholm, Sweden, 14186
      • Uppsala, Sweden, 75185
  • United Kingdom
      • Middlesbrough, United Kingdom, TS4 3BW
      • Swansea, United Kingdom, SA6 6NL
    • County Antrim
      • Belfast, County Antrim, United Kingdom, BT9 7AB
    • Devon
      • Exeter, Devon, United Kingdom, EX2 5DW
    • East Riding Of Yorkshire
      • Hull, East Riding Of Yorkshire, United Kingdom, HU3 2JZ
    • East Sussex
      • Brighton, East Sussex, United Kingdom, BN2 5BE
    • Greater London
      • London, Greater London, United Kingdom, SE5 9RS
      • London, Greater London, United Kingdom, NW3 2QG
      • London, Greater London, United Kingdom, SW17 0QT
    • Greater Manchester
      • Manchester, Greater Manchester, United Kingdom, M13 9WL
      • Salford, Greater Manchester, United Kingdom, M6 8HD
    • Hertfordshire
      • Stevenage, Hertfordshire, United Kingdom, SG1 4AB
    • Highland Region
      • Inverness, Highland Region, United Kingdom, IV2 3UJ
    • Leicestershire
      • Leicester, Leicestershire, United Kingdom, LE5 4PW
    • Lothian Region
      • Edinburgh, Lothian Region, United Kingdom, EH16 4SA
    • Norfolk
      • Liverpool, Norfolk, United Kingdom, L7 8XP
    • South Yorkshire
      • Sheffield, South Yorkshire, United Kingdom, S5 7AU
    • Staffordshire
      • Stoke on Trent, Staffordshire, United Kingdom, ST4 7LN
    • Tyne & Wear
      • Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE7 7DN
    • Warwickshire
      • Coventry, Warwickshire, United Kingdom, CV2 2DX
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B15 2GW
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
      • Huntsville, Alabama, United States, 35805
      • Mobile, Alabama, United States, 36617
    • Arizona
      • Phoenix, Arizona, United States, 85381
      • Tempe, Arizona, United States, 85284
      • Tucson, Arizona, United States, 85745
    • California
      • La Jolla, California, United States, 92037
      • Los Angeles, California, United States, 90095
      • Los Angeles, California, United States, 90022
      • San Francisco, California, United States, 94143
      • Stanford, California, United States, 94305
    • Colorado
      • Aurora, Colorado, United States, 80045
      • Denver, Colorado, United States, 80204
      • Denver, Colorado, United States, 80210
    • Connecticut
      • New Haven, Connecticut, United States, 06520
    • Florida
      • Hudson, Florida, United States, 34667
      • Jacksonville, Florida, United States, 32216
      • Miami, Florida, United States, 33150
      • Ocala, Florida, United States, 34471
      • Port Charlotte, Florida, United States, 33952
      • Tampa, Florida, United States, 33614
    • Georgia
      • Atlanta, Georgia, United States, 30322
      • Augusta, Georgia, United States, 30909
    • Idaho
      • Meridian, Idaho, United States, 83642
    • Illinois
      • Chicago, Illinois, United States, 60637
      • Chicago, Illinois, United States, 60611
    • Kansas
      • Kansas City, Kansas, United States, 66160
      • Wichita, Kansas, United States, 67214
    • Louisiana
      • Baton Rouge, Louisiana, United States, 70808
    • Maryland
      • Baltimore, Maryland, United States, 21224
      • Baltimore, Maryland, United States, 21201
      • Greenbelt, Maryland, United States, 20770
      • Rockville, Maryland, United States, 20850
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
      • Springfield, Massachusetts, United States, 01107
    • Michigan
      • Detroit, Michigan, United States, 48202
      • Grand Rapids, Michigan, United States, 49506
      • Kalamazoo, Michigan, United States, 49007
      • Pontiac, Michigan, United States, 48341
      • Roseville, Michigan, United States, 48066
    • Minnesota
      • Rochester, Minnesota, United States, 55905
    • Missouri
      • Saint Louis, Missouri, United States, 63110
    • Nevada
      • Las Vegas, Nevada, United States, 89106
      • Reno, Nevada, United States, 89511
    • New Jersey
      • Eatontown, New Jersey, United States, 07724
      • Voorhees, New Jersey, United States, 08043
    • New York
      • Buffalo, New York, United States, 14219
      • Laurelton, New York, United States, 11413
      • Mineola, New York, United States, 11501
      • New York, New York, United States, 10032
      • New York, New York, United States, 10021
    • North Carolina
      • Asheville, North Carolina, United States, 28801
      • Chapel Hill, North Carolina, United States, 27599
      • Charlotte, North Carolina, United States, 28207
      • Winston-Salem, North Carolina, United States, 27103
    • North Dakota
      • Fargo, North Dakota, United States, 58102
    • Ohio
      • Akron, Ohio, United States, 44302
      • Cincinnati, Ohio, United States, 45229
      • Cincinnati, Ohio, United States, 45206
      • Cleveland, Ohio, United States, 44106
      • Columbus, Ohio, United States, 43210
    • Oregon
      • Portland, Oregon, United States, 97210
    • Pennsylvania
      • Bethlehem, Pennsylvania, United States, 18017
      • Doylestown, Pennsylvania, United States, 18901
      • Philadelphia, Pennsylvania, United States, 19104
    • South Carolina
      • Charleston, South Carolina, United States, 29425
      • Columbia, South Carolina, United States, 29203
      • Orangeburg, South Carolina, United States, 29118
    • Tennessee
      • Knoxville, Tennessee, United States, 37923
      • Nashville, Tennessee, United States, 37232
      • Nashville, Tennessee, United States, 37205
    • Texas
      • Arlington, Texas, United States, 76015
      • Houston, Texas, United States, 77030
      • Houston, Texas, United States, 77004
      • McAllen, Texas, United States, 78503
    • Vermont
      • Burlington, Vermont, United States, 05401
    • Virginia
      • Arlington, Virginia, United States, 22207
      • Charlottesville, Virginia, United States, 22908
      • Norfolk, Virginia, United States, 23507
    • Washington
      • Wenatchee, Washington, United States, 98801
    • West Virginia
      • Morgantown, West Virginia, United States, 26506

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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
Other Names:
  • OPC-41061

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment(+ 7 days)
An adverse event (AE) was as any untoward medical occurrence associated with the use of an investigational medicinal product (IMP), whether or not considered IMP related. A TEAE was an AE that started after trial drug treatment; or if the event was continuous from baseline and was serious, related to IMP, or resulted in death, discontinuation, interruption or reduction of trial therapy. A serious TEAE included any event that resulted in: death, life-threatening, persistent or significant incapacity, substantial disruption of ability to conduct normal life functions, required inpatient hospitalization, prolonged hospitalization, congenital anomaly/birth defect, or other medically significant events as per medical judgment, that jeopardized the participant and that required medical or surgical intervention. A severe TEAE was an inability to work or perform normal daily activity. A summary of serious and all other non-serious TEAEs, regardless of causality, is located in the AE section.
Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment(+ 7 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2014

Primary Completion (Actual)

November 9, 2018

Study Completion (Actual)

November 9, 2018

Study Registration Dates

First Submitted

September 25, 2014

First Submitted That Met QC Criteria

September 25, 2014

First Posted (Estimate)

September 29, 2014

Study Record Updates

Last Update Posted (Actual)

November 27, 2019

Last Update Submitted That Met QC Criteria

November 7, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 156-13-211

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

IPD Sharing Time Frame

Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.

IPD Sharing Access Criteria

Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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