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
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
1 other identifier
interventional
1,370
22 countries
230
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)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started May 2014
Typical duration for phase_3
230 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2014
CompletedFirst Submitted
Initial submission to the registry
June 6, 2014
CompletedFirst Posted
Study publicly available on registry
June 10, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 18, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
April 18, 2017
CompletedResults Posted
Study results publicly available
August 8, 2018
CompletedAugust 8, 2018
July 1, 2018
3 years
June 6, 2014
May 1, 2018
July 13, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The Mean Annualized Change in eGFR From Pretreatment Baseline to Post-treatment Follow-up.
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.
Pretreatment baseline to post-treatment follow-up (up to 61 weeks).
Secondary Outcomes (1)
Mean Annualized Slope of eGFR Change
Pretreatment baseline to post-treatment follow-up (up to 61 weeks).
Other Outcomes (2)
Mean Change From Baseline in Urine Osmolality During the Double-blind Treatment Period and Post-treatment Follow-up
Baseline and Months 3, 6, 9 and 12 (End of treatment visit) of the double-blind treatment period, and post-treatment follow-up.
Mean Change From Baseline in Urine Specific Gravity During the Double-blind Treatment Period and Post-treatment Follow-up
Baseline and Months 3, 6, 9 and 12 (End of treatment visit) of the double-blind treatment period, and post-treatment follow-up.
Study Arms (2)
Tolvaptan
EXPERIMENTALTolvaptan (OPC-41061)
Placebo
PLACEBO COMPARATORPlacebo
Interventions
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.
Matching placebo tablets will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (230)
Unknown Facility
Birmingham, Alabama, 35294, United States
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Huntsville, Alabama, 35805, United States
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Mobile, Alabama, 36617, United States
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Phoenix, Arizona, 85381, United States
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Tempe, Arizona, 85284, United States
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Tucson, Arizona, 85745, United States
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La Jolla, California, 92037, United States
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Los Angeles, California, 90022, United States
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Los Angeles, California, 90025, United States
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San Francisco, California, 94143, United States
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Aurora, Colorado, 80045, United States
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Denver, Colorado, 80210, United States
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New Haven, Connecticut, 06520, United States
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Hudson, Florida, 34667, United States
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Jacksonville, Florida, 32216, United States
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Miami, Florida, 33150, United States
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Ocala, Florida, 34471, United States
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Port Charlotte, Florida, 33952, United States
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Tampa, Florida, 33614, United States
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Atlanta, Georgia, 30322, United States
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Augusta, Georgia, 30909, United States
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Meridian, Idaho, 83642, United States
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Chicago, Illinois, 60637, United States
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Kansas City, Kansas, 66160, United States
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Wichita, Kansas, 67214, United States
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Baton Rouge, Louisiana, 70808, United States
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Lafayette, Louisiana, 70503, United States
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Baltimore, Maryland, 21201, United States
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Greenbelt, Maryland, 20770, United States
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Rockville, Maryland, 20850, United States
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Wheaton, Maryland, 20906, United States
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Boston, Massachusetts, 02215, United States
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Springfield, Massachusetts, 01107, United States
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Detroit, Michigan, 48202, United States
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Kalamazoo, Michigan, 49007, United States
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Pontiac, Michigan, 48341, United States
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Roseville, Michigan, 48066, United States
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Minneapolis, Minnesota, 55404, United States
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Rochester, Minnesota, 55905, United States
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St Louis, Missouri, 63110, United States
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Las Vegas, Nevada, 89128, United States
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Reno, Nevada, 89511, United States
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Eatontown, New Jersey, 07724, United States
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Voorhees Township, New Jersey, 08043, United States
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Buffalo, New York, 14215, United States
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Mineola, New York, 11501, United States
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New York, New York, 10016, United States
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New York, New York, 10021, United States
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New York, New York, 10032, United States
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Rosedale, New York, 11422, United States
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Asheville, North Carolina, 28801, United States
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Chapel Hill, North Carolina, 27599-7155, United States
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Charlotte, North Carolina, 28207, United States
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Winston-Salem, North Carolina, 27103, United States
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Fargo, North Dakota, 58122, United States
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Grand Forks, North Dakota, 58201, United States
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Akron, Ohio, 44302, United States
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Cincinnati, Ohio, 45206, United States
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Cleveland, Ohio, 44106, United States
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Cleveland, Ohio, 44195, United States
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Columbus, Ohio, 43210, United States
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Portland, Oregon, 98686, United States
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Bethlehem, Pennsylvania, 18017, United States
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Doylestown, Pennsylvania, 18901, United States
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Philadelphia, Pennsylvania, 19104, United States
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Charleston, South Carolina, 29425, United States
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Columbia, South Carolina, 29203, United States
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Orangeburg, South Carolina, 29118, United States
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Knoxville, Tennessee, 39723, United States
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Nashville, Tennessee, 37205, United States
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Nashville, Tennessee, 37232, United States
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Arlington, Texas, 76015, United States
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Houston, Texas, 77030-3411, United States
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Houston, Texas, 77030, United States
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McAllen, Texas, 78503, United States
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Burlington, Vermont, 05401, United States
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Arlington, Virginia, 22205, United States
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Charlottesville, Virginia, 22908, United States
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Norfolk, Virginia, 23507, United States
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Wenatchee, Washington, 98801, United States
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Morgantown, West Virginia, 26506, United States
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La Crosse, Wisconsin, 54601, United States
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Bahía Blanca, Buenos Aires, B8000FTD, Argentina
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Ciudad Autonoma, Buenos Aires, C1093AAS, Argentina
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Ciudad Autonoma, Buenos Aires, C1119ACN, Argentina
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Ciudad Autonoma, Buenos Aires, C1425APQ, Argentina
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Ciudad Autonoma, Buenos Aires, C1429BWN, Argentina
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Ciudad Autonoma, Buenos Aires, C1431FWO, Argentina
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Junín, Buenos Aires, 6000, Argentina
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Pergamino, Buenos Aires, B2700CPM, Argentina
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Pilar, Buenos Aires, B1629ODT, Argentina
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Sarandí, Buenos Aires, B1872EEA, Argentina
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Córdoba, X5000JHQ, Argentina
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Córdoba, X5003DCE, Argentina
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Córdoba, X5016KEH, Argentina
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Camperdown, New South Wales, 2050, Australia
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Concord, New South Wales, 2139, Australia
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New Lambton Heights, New South Wales, 2305, Australia
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St Leonards, New South Wales, 2065, Australia
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Westmead, New South Wales, 2145, Australia
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Woolloongabba, Queensland, 4102, Australia
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Adelaide, South Australia, 5000, Australia
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Launceston, Tasmania, 7250, Australia
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Parkville, Victoria, 3050, Australia
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Reservoir, Victoria, 3073, Australia
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Richmond, Victoria, 3121, Australia
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Perth, Western Australia, 6000, Australia
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Aalst, 9300, Belgium
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Antwerp, 2650, Belgium
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Brussels, 1090, Belgium
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Brussels, 1200, Belgium
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Ghent, 9000, Belgium
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Kortrijk, 8500, Belgium
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Leuven, 3000, Belgium
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Liège, 400, Belgium
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Edmonton, Alberta, T6G 2B7, Canada
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St. John's, Newfoundland and Labrador, A1B 3V6, Canada
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Scarborough Village, Ontario, M1H 3G4, Canada
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Toronto, Ontario, M4C 5T2, Canada
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Toronto, Ontario, M5C 2T2, Canada
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Toronto, Ontario, M5G 2N2, Canada
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Greenfield Park, Quebec, J4V 2H1, Canada
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Montreal, Quebec, H3A 1A1, Canada
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Montreal, Quebec, H4J 1C5, Canada
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Brno, 625 00, Czechia
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České Budějovice, 370 01, Czechia
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Hradec Králové, 500 05, Czechia
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Jihlava, 586 33, Czechia
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Jilemnice, 51401, Czechia
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Liberec, 460 63, Czechia
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Ostrava, 708 52, Czechia
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Prague, 128 08, Czechia
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Prague, 140 21, Czechia
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Tábor, 390 03, Czechia
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Aalborg, 9100, Denmark
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Aarhus C, 8000, Denmark
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Holstebro, 7500, Denmark
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Odense C, 5000, Denmark
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Viborg, 8800, Denmark
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Brest, Finistere, 29609, France
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Bordeaux, Gironde, 33000, France
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Toulouse, Haute Garonne, 31059, France
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Montpellier, Herault, 34295, France
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Grenoble, Isere, 38043, France
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Reims, Marne, 51090, France
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Vandœuvre-lès-Nancy, Meurthe Et Moselle, 54511, France
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Saint-Priest-En-Jarez, Pays de la Loire Region, 42055, France
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Lyon, Rhone, 69437, France
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Pierre-Bénite, Rhone, 69495, France
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Heidelberg, Baden-Wurttemberg, 69120, Germany
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Munich, Bavaria, 81675, Germany
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Nuremberg, Bavaria, 90471, Germany
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Hanover, Lower Saxony, 30625, Germany
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Düsseldorf, North Rhine-Westphalia, 40210, Germany
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Essen, North Rhine-Westphalia, 45147, Germany
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Wiesbaden, North Rhine-Westphalia, 65191, Germany
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Dresden, Saxony, 01307, Germany
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Budapest, 1032, Hungary
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Pécs, 7623, Hungary
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Szeged, 6720, Hungary
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Ashkelon, 7830604, Israel
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Jerusalem, 9112001, Israel
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Nahariya, 22100, Israel
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Petah Tikva, 4941492, Israel
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Ramat Gan, 52621, Israel
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Tel Aviv, 34239, Israel
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Torrette Di Ancona, Ancona, 60126, Italy
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Montichiari, Brescia, 25018, Italy
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Bari, 70124, Italy
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Bologna, 40138, Italy
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Lecco, 23900, Italy
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Milan, 20122, Italy
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Milan, 20132, Italy
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Modena, 41124, Italy
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Napoli, 80131, Italy
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Pavia, 27100, Italy
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Groningen, 9713 GZ, Netherlands
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Nijmegen, 6525 GA, Netherlands
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Bergen, 5021, Norway
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Oslo, 0424, Norway
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Stavanger, 4068, Norway
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Ciechanów, 06-400, Poland
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Golub-Dobrzyń, 87-400, Poland
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Krakow, 31-559, Poland
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Lodz, 92-213, Poland
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Lodz, 92-313, Poland
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Lublin, 20-954, Poland
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Warsaw, 04-749, Poland
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Wroclaw, 50-556, Poland
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San Juan, 00918, Puerto Rico
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Bucharest, 011794, Romania
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Bucharest, 022328, Romania
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Oradea, 410649, Romania
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Krasnoyarsk, 660062, Russia
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Saint Petersburg, 194044, Russia
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Saint Petersburg, 197110, Russia
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Yaroslavl, 150062, Russia
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Pretoria, Gauteng, 0002, South Africa
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Durban, KwaZulu-Natal, 4001, South Africa
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Cape Town, Western Cape, 7925, South Africa
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L'Hospitalet de Llobregat, Barcelona, 08907, Spain
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Ciudad Real, 13005, Spain
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Madrid, 28041, Spain
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Madrid, 28046, Spain
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Seville, 41009, Spain
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Seville, 41071, Spain
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Valencia, 46017, Spain
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Gothenburg, 41345, Sweden
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Linköping, 58185, Sweden
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Örebro, 70185, Sweden
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Stockholm, 141 86, Sweden
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Stockholm, 14186, Sweden
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Uppsala, 75185, Sweden
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Exeter, Devon, EX2 5DW, United Kingdom
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Hull, East Riding Of Yorkshire, HU3 2JZ, United Kingdom
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Brighton, East Sussex, BN2 5BE, United Kingdom
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London, Greater London, NW3 2QG, United Kingdom
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Manchester, Greater Manchester, M13 9WL, United Kingdom
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Salford, Greater Manchester, M6 8HD, United Kingdom
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Stevenage, Hertfordshire, SG1 4AB, United Kingdom
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Inverness, Highland Region, IV2 3UJ, United Kingdom
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Leicester, Leicestershire, LE5 4PW, United Kingdom
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Edinburgh, Lothian Region, EH16 4SA, United Kingdom
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Liverpool, Merseyside, L7 8XP, United Kingdom
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Middlesbrough, North Yorkshire, TS4 3BW, United Kingdom
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Sheffield, South Yorkshire, S5 7AU, United Kingdom
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Stoke-on-Trent, Staffordshire, ST4 6QG, United Kingdom
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Newcastle upon Tyne, Tyne & Wear, NE7 7DN, United Kingdom
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Coventry, Warwickshire, CV2 2DX, United Kingdom
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Swansea, SA6 6NL, United Kingdom
Related Publications (5)
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: 39356039DERIVEDChebib 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: 37250503DERIVEDAlpers 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.
PMID: 36191725DERIVEDBennett H, McEwan P, Hamilton K, O'Reilly K. Modelling the long-term benefits of tolvaptan therapy on renal function decline in autosomal dominant polycystic kidney disease: an exploratory analysis using the ADPKD outcomes model. BMC Nephrol. 2019 Apr 23;20(1):136. doi: 10.1186/s12882-019-1290-5.
PMID: 31014270DERIVEDTorres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Koch G, Ouyang J, McQuade RD, Blais JD, Czerwiec FS, Sergeyeva O; REPRISE Trial Investigators. Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. N Engl J Med. 2017 Nov 16;377(20):1930-1942. doi: 10.1056/NEJMoa1710030. Epub 2017 Nov 4.
PMID: 29105594DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Devlopment
- Organization
- Otsuka Pharmaceutical Development & Commercialization, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 6, 2014
First Posted
June 10, 2014
Study Start
May 1, 2014
Primary Completion
April 18, 2017
Study Completion
April 18, 2017
Last Updated
August 8, 2018
Results First Posted
August 8, 2018
Record last verified: 2018-07