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

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

Sponsors

Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Source Otsuka Pharmaceutical Development & Commercialization, Inc.
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).

Overall Status Completed
Start Date October 17, 2014
Completion Date November 9, 2018
Primary Completion Date November 9, 2018
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Number Of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) Baseline through end of treatment (up to 42 months) and follow-up 7 days posttreatment(+ 7 days)
Enrollment 1803
Condition
Intervention

Intervention type: Drug

Intervention name: Tolvaptan

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

Arm group label: Tolvaptan

Other name: 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

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

Argentina

Australia

Belgium

Canada

Czechia

Denmark

Germany

Hungary

Israel

Italy

Netherlands

Norway

Poland

Romania

Russian Federation

South Africa

Spain

Sweden

United Kingdom

United States

Verification Date

November 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Tolvaptan

Arm group type: Experimental

Description: 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.

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov