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Efficacy and Safety of Tolvaptan in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease

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ClinicalTrials.gov Identifier: NCT02160145
Recruitment Status : Completed
First Posted : June 10, 2014
Results First Posted : August 8, 2018
Last Update Posted : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary:
The purpose of the study is to determine whether tolvaptan is effective and safe for the treatment of late-stage chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD)

Condition or disease Intervention/treatment Phase
Chronic Kidney Disease Autosomal Dominant Polycystic Kidney Disease Drug: Tolvaptan (OPC-41061) Drug: Placebo Phase 3

Detailed Description:

The protocol will extend the understanding of the efficacy and safety of tolvaptan treatment in ADPKD patients with late stage 2 to early stage 4 CKD (chronic kidney disease).

This trial will compare the efficacy of tolvaptan treatment in reducing the annualized change in estimated glomerular filtration rate (eGFR) from pre-treatment baseline to post-treatment follow-up, as compared with placebo, in subjects who tolerate tolvaptan during an initial run-in period. The change in eGFR, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula, will provide kidney function data that are complementary to the data demonstrating the benefits previously observed primarily in ADPKD subjects with earlier stages of disease.

Also, it will compare the efficacy of tolvaptan treatment in reducing the decline of annualized eGFR slope, as compared with placebo, in this type of subjects. Finally, it will compare the overall and hepatic safety profile of tolvaptan with placebo and to compare incidence of ADPKD complications (outcomes) during the trial


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1370 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3b, Multi-center, Randomized-withdrawal, Placebo-controlled, Double-blind, Parallel-group Trial to Compare the Efficacy and Safety of Tolvaptan (45 to 120 mg/Day, Split-dose) in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease
Study Start Date : May 2014
Actual Primary Completion Date : April 18, 2017
Actual Study Completion Date : April 18, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases
Drug Information available for: Tolvaptan

Arm Intervention/treatment
Experimental: Tolvaptan
Tolvaptan (OPC-41061)
Drug: Tolvaptan (OPC-41061)
Tolvaptan tablets (15 or 30 mg) will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later.

Placebo Comparator: Placebo
Placebo
Drug: Placebo
Matching placebo tablets will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later




Primary Outcome Measures :
  1. The Mean Annualized Change in eGFR From Pretreatment Baseline to Post-treatment Follow-up. [ Time Frame: Pretreatment baseline to post-treatment follow-up (up to 61 weeks). ]

    The mean annualized change in eGFR was calculated using the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula from pretreatment baseline to post-treatment follow-up, annualized (divided) by each subject's trial duration.

    The baseline for the primary endpoint was defined as the average of up to 3 eGFR values observed during the screening and placebo run-in periods.



Secondary Outcome Measures :
  1. Mean Annualized Slope of eGFR Change [ Time Frame: Pretreatment baseline to post-treatment follow-up (up to 61 weeks). ]

    To compare the efficacy of tolvaptan treatment in reducing the decline of annualized eGFR slope, as compared with placebo, in subjects with late-stage CKD due to ADPKD who tolerated tolvaptan during an initial run-in period, the annualized rate of eGFR change was derived from each individual subject's eGFR slope using the CKD-EPI formula.

    The annualized eGFR change slope was derived from all eGFR observations from placebo-run-in, tolvaptan run-in, double-blind treatment and post-treatment follow-up periods using the linear mixed model of analysis. The mean annualized slope of eGFR change is presented.



Other Outcome Measures:
  1. Mean Change From Baseline in Urine Osmolality During the Double-blind Treatment Period and Post-treatment Follow-up [ Time Frame: Baseline and Months 3, 6, 9 and 12 (End of treatment visit) of the double-blind treatment period, and post-treatment follow-up. ]
    The mean change from baseline in urine osmolality for the double-blind treatment period collection timepoints and post-treatment follow-up are presented. Baseline was defined as the last evaluation prior to post-randomization dosing.

  2. Mean Change From Baseline in Urine Specific Gravity During the Double-blind Treatment Period and Post-treatment Follow-up [ Time Frame: Baseline and Months 3, 6, 9 and 12 (End of treatment visit) of the double-blind treatment period, and post-treatment follow-up. ]
    The mean change from baseline in urine specific gravity for the double-blind treatment period collection timepoints and post-treatment follow up are presented. Baseline was defined as the last evaluation prior to post-randomization dosing.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects with eGFR between 25-65 mL/min/1.73m2 (if aged 18 to55) or eGFR between 25-44 mL/min/1.73m2 (if aged 56 to <66)
  • Tolvaptan naïve
  • Diagnosis of ADPKD by modified pei-Ravine criteria 1) 3 cysts per kidney by sonography or 5 cysts by CT or MRI with family history of ADPKD or 2) 10 cysts per kidney by any radiologic method and exclusion of other cystic kidney diseases if without family history

Exclusion Criteria:

  • 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 prior to receiving IMP
  • Need for chronic diuretic use
  • Hepatic impairment or liver function abnormalities other than that expected for ADPKD with typical cystic liver disease
  • Advanced diabetes, evidence of additional significant renal disease, renal cancer, single kidney, recent renal surgery or acute kidney injury
  • Contraindications to required trial assessments
  • Medical history or medical findings inconsistent with safety or compliance with trial assessments

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02160145


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Locations
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United States, Alabama
Birmingham, Alabama, United States, 35294
Huntsville, Alabama, United States, 35805
Mobile, Alabama, United States, 36617
United States, Arizona
Phoenix, Arizona, United States, 85381
Tempe, Arizona, United States, 85284
Tucson, Arizona, United States, 85745
United States, California
La Jolla, California, United States, 92037
Los Angeles, California, United States, 90022
Los Angeles, California, United States, 90025
San Francisco, California, United States, 94143
United States, Colorado
Aurora, Colorado, United States, 80045
Denver, Colorado, United States, 80210
United States, Connecticut
New Haven, Connecticut, United States, 06520
United States, 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
United States, Georgia
Atlanta, Georgia, United States, 30322
Augusta, Georgia, United States, 30909
United States, Idaho
Meridian, Idaho, United States, 83642
United States, Illinois
Chicago, Illinois, United States, 60637
United States, Kansas
Kansas City, Kansas, United States, 66160
Wichita, Kansas, United States, 67214
United States, Louisiana
Baton Rouge, Louisiana, United States, 70808
Lafayette, Louisiana, United States, 70503
United States, Maryland
Baltimore, Maryland, United States, 21201
Greenbelt, Maryland, United States, 20770
Rockville, Maryland, United States, 20850
Wheaton, Maryland, United States, 20906
United States, Massachusetts
Boston, Massachusetts, United States, 02215
Springfield, Massachusetts, United States, 01107
United States, Michigan
Detroit, Michigan, United States, 48202
Kalamazoo, Michigan, United States, 49007
Pontiac, Michigan, United States, 48341
Roseville, Michigan, United States, 48066
United States, Minnesota
Minneapolis, Minnesota, United States, 55404
Rochester, Minnesota, United States, 55905
United States, Missouri
Saint Louis, Missouri, United States, 63110
United States, Nevada
Las Vegas, Nevada, United States, 89128
Reno, Nevada, United States, 89511
United States, New Jersey
Eatontown, New Jersey, United States, 07724
Voorhees, New Jersey, United States, 08043
United States, New York
Buffalo, New York, United States, 14215
Mineola, New York, United States, 11501
New York, New York, United States, 10016
New York, New York, United States, 10021
New York, New York, United States, 10032
Rosedale, New York, United States, 11422
United States, North Carolina
Asheville, North Carolina, United States, 28801
Chapel Hill, North Carolina, United States, 27599-7155
Charlotte, North Carolina, United States, 28207
Winston-Salem, North Carolina, United States, 27103
United States, North Dakota
Fargo, North Dakota, United States, 58122
Grand Forks, North Dakota, United States, 58201
United States, Ohio
Akron, Ohio, United States, 44302
Cincinnati, Ohio, United States, 45206
Cleveland, Ohio, United States, 44106
Cleveland, Ohio, United States, 44195
Columbus, Ohio, United States, 43210
United States, Oregon
Portland, Oregon, United States, 98686
United States, Pennsylvania
Bethlehem, Pennsylvania, United States, 18017
Doylestown, Pennsylvania, United States, 18901
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
Charleston, South Carolina, United States, 29425
Columbia, South Carolina, United States, 29203
Orangeburg, South Carolina, United States, 29118
United States, Tennessee
Knoxville, Tennessee, United States, 39723
Nashville, Tennessee, United States, 37205
Nashville, Tennessee, United States, 37232
United States, Texas
Arlington, Texas, United States, 76015
Houston, Texas, United States, 77030-3411
Houston, Texas, United States, 77030
McAllen, Texas, United States, 78503
United States, Vermont
Burlington, Vermont, United States, 05401
United States, Virginia
Arlington, Virginia, United States, 22205
Charlottesville, Virginia, United States, 22908
Norfolk, Virginia, United States, 23507
United States, Washington
Wenatchee, Washington, United States, 98801
United States, West Virginia
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
La Crosse, Wisconsin, United States, 54601
Argentina
Bahia Blanca, Buenos Aires, Argentina, B8000FTD
Ciudad Autonoma, Buenos Aires, Argentina, C1093AAS
Ciudad Autonoma, Buenos Aires, Argentina, C1119ACN
Ciudad Autonoma, Buenos Aires, Argentina, C1425APQ
Ciudad Autonoma, Buenos Aires, Argentina, C1429BWN
Ciudad Autonoma, Buenos Aires, Argentina, C1431FWO
Junin, Buenos Aires, Argentina, 6000
Pergamino, Buenos Aires, Argentina, B2700CPM
Pilar, Buenos Aires, Argentina, B1629ODT
Sarandi, Buenos Aires, Argentina, B1872EEA
Cordoba, Argentina, X5000JHQ
Cordoba, Argentina, X5003DCE
Cordoba, Argentina, X5016KEH
Australia, New South Wales
Camperdown, New South Wales, Australia, 2050
Concord, New South Wales, Australia, 2139
New Lambton Heights, New South Wales, Australia, 2305
St. Leonards, New South Wales, Australia, 2065
Westmead, New South Wales, Australia, 2145
Australia, Queensland
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Adelaide, South Australia, Australia, 5000
Australia, Tasmania
Launceston, Tasmania, Australia, 7250
Australia, Victoria
Parkville, Victoria, Australia, 3050
Reservoir, Victoria, Australia, 3073
Richmond, Victoria, Australia, 3121
Australia, Western Australia
Perth, Western Australia, Australia, 6000
Belgium
Aalst, Belgium, 9300
Antwerpen, Belgium, 2650
Bruxelles, Belgium, 1090
Bruxelles, Belgium, 1200
Gent, Belgium, 9000
Kortrijk, Belgium, 8500
Leuven, Belgium, 3000
Liège, Belgium, 400
Canada, Alberta
Edmonton, Alberta, Canada, T6G 2B7
Canada, Newfoundland and Labrador
St. John's, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Scarborough, Ontario, Canada, M1H 3G4
Toronto, Ontario, Canada, M4C 5T2
Toronto, Ontario, Canada, M5C 2T2
Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
Greenfield Park, Quebec, Canada, J4V 2H1
Montreal, Quebec, Canada, H3A 1A1
Montréal, Quebec, Canada, H4J 1C5
Czechia
Brno, Czechia, 625 00
Ceske Budejovice, Czechia, 370 01
Hradec Kralove, Czechia, 500 05
Jihlava, Czechia, 586 33
Jilemnice, Czechia, 51401
Liberec, Czechia, 460 63
Ostrava, Czechia, 708 52
Praha 2, Czechia, 128 08
Praha 4, Czechia, 140 21
Tabor, Czechia, 390 03
Denmark
Aalborg, Denmark, 9100
Aarhus C, Denmark, 8000
Holstebro, Denmark, 7500
Odense C, Denmark, 5000
Viborg, Denmark, 8800
France
Brest cedex 2, Finistere, France, 29609
Bordeaux Cedex, Gironde, France, 33000
Toulouse Cedex 9, Haute Garonne, France, 31059
Montpellier cedex 5, Herault, France, 34295
Grenoble cedex 9, Isere, France, 38043
Saint-Priest-En-Jarez, Loire, France, 42055
Reims Cedex, Marne, France, 51090
Vandoeuvre les Nancy, Meurthe Et Moselle, France, 54511
Lyon Cedex 03, Rhone, France, 69437
Pierre-Bénite cedex, Rhone, France, 69495
Germany
Heidelberg, Baden Wuerttemberg, Germany, 69120
Muenchen, Bayern, Germany, 81675
Nuernberg, Bayern, Germany, 90471
Hannover, Niedersachsen, Germany, 30625
Duesseldorf, Nordrhein Westfalen, Germany, 40210
Essen, Nordrhein Westfalen, Germany, 45147
Wiesbaden, Nordrhein Westfalen, Germany, 65191
Dresden, Sachsen, Germany, 01307
Hungary
Budapest, Hungary, 1032
Pecs, Hungary, 7623
Szeged, Hungary, 6720
Israel
Ashkelon, Israel, 7830604
Jerusalem, Israel, 9112001
Nahariya, Israel, 22100
Petach Tikva, Israel, 4941492
Petaẖ Tiqwa, Israel, 4941492
Ramat-Gan, Israel, 52621
Tel Aviv, Israel, 34239
Italy
Torrette Di Ancona, Ancona, Italy, 60126
Montichiari, Brescia, Italy, 25018
Bari, Italy, 70124
Bologna, Italy, 40138
Lecco, Italy, 23900
Milano, Italy, 20122
Milano, Italy, 20132
Modena, Italy, 41124
Napoli, Italy, 80131
Pavia, Italy, 27100
Netherlands
Groningen, Netherlands, 9713 GZ
Nijmegen, Netherlands, 6525 GA
Norway
Bergen, Norway, 5021
Oslo, Norway, 0424
Stavanger, Norway, 4068
Poland
Ciechanow, Poland, 06-400
Golub Dobrzyn, Poland, 87-400
Kraków, Poland, 31-559
Lodz, Poland, 92-213
Lublin, Poland, 20-954
Warszawa, Poland, 04-749
Wroclaw, Poland, 50-556
Łódź, Poland, 92-313
Puerto Rico
San Juan, Puerto Rico, 00918
Romania
Bucuresti, Romania, 011794
Bucuresti, Romania, 022328
Oradea, Romania, 410649
Russian Federation
Krasnoyarsk, Russian Federation, 660062
St. Petersburg, Russian Federation, 194044
St. Petersburg, Russian Federation, 197110
Yaroslavl, Russian Federation, 150062
South Africa
Pretoria, Gauteng, South Africa, 0002
Durban, KwaZulu-Natal, South Africa, 4001
Cape Town, Western Cape, South Africa, 7925
Spain
L'Hospitalet de Llobregat, Barcelona, Spain, 08907
Ciudad Real, Spain, 13005
Madrid, Spain, 28041
Madrid, Spain, 28046
Sevilla, Spain, 41009
Sevilla, Spain, 41071
Valencia, Spain, 46017
Sweden
Göteborg, Sweden, 41345
Linköping, Sweden, 58185
Stockholm, Sweden, 141 86
Stockholm, Sweden, 14186
Uppsala, Sweden, 75185
Örebro, Sweden, 70185
United Kingdom
Exeter, Devon, United Kingdom, EX2 5DW
Hull, East Riding Of Yorkshire, United Kingdom, HU3 2JZ
Brighton, East Sussex, United Kingdom, BN2 5BE
London, Greater London, United Kingdom, NW3 2QG
Manchester, Greater Manchester, United Kingdom, M13 9WL
Salford, Greater Manchester, United Kingdom, M6 8HD
Stevenage, Hertfordshire, United Kingdom, SG1 4AB
Inverness, Highland Region, United Kingdom, IV2 3UJ
Leicester, Leicestershire, United Kingdom, LE5 4PW
Edinburgh, Lothian Region, United Kingdom, EH16 4SA
Liverpool, Merseyside, United Kingdom, L7 8XP
Middlesbrough, North Yorkshire, United Kingdom, TS4 3BW
Sheffield, South Yorkshire, United Kingdom, S5 7AU
Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QG
Newcastle upon Tyne, Tyne & Wear, United Kingdom, NE7 7DN
Coventry, Warwickshire, United Kingdom, CV2 2DX
Swansea, United Kingdom, SA6 6NL
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
  Study Documents (Full-Text)

Documents provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Statistical Analysis Plan  [PDF] March 31, 2017
Study Protocol  [PDF] March 26, 2015


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02160145     History of Changes
Other Study ID Numbers: 156-13-210
First Posted: June 10, 2014    Key Record Dates
Results First Posted: August 8, 2018
Last Update Posted: August 8, 2018
Last Verified: July 2018

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Chronic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease

Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Renal Insufficiency
Kidney Diseases, Cystic
Abnormalities, Multiple
Congenital Abnormalities
Ciliopathies
Genetic Diseases, Inborn
Tolvaptan
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Natriuretic Agents
Physiological Effects of Drugs