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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT02160145
First received: June 6, 2014
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Chronic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease
Drug: Tolvaptan (OPC-41061)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Treatment difference in the change of eGFR from pre-treatment baseline to post-treatment follow-up, normalized (divided) by each subject's treatment duration [ Time Frame: prior to and post 13 1/2 months of treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment difference in annualized slope of eGFR calculated for individual subjects using an appropriate baseline and available, post-randomization, on-treatment assessments [ Time Frame: prior to and post 13 1/2 months of treatment ] [ Designated as safety issue: No ]
  • Plasma tolvaptan and metabolites, including DM-4103 plasma concentrations [ Time Frame: Day -1 through Month 15 1/2 ] [ Designated as safety issue: No ]
  • Uosm and urine specific gravity [ Time Frame: Day -1 through Month 15 1/2 ] [ Designated as safety issue: No ]

Estimated Enrollment: 1300
Study Start Date: May 2014
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 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 be compared 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 be compared the overall and hepatic safety profile of tolvaptan with placebo and to compare incidence of ADPKD complications (outcomes) during the trial

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02160145

Contacts
Contact: - - - Reprisestudy@mmgct.com

Locations
United States, Arizona
Arizona Kidney Disease and Hypertension Center Recruiting
Peoria, Arizona, United States, 85381
Contact: Jessica Bartlett    602-351-3928    jbartlett@akdhc.com   
Principal Investigator: Raul Rodelas         
United States, California
Scripps Clinic Recruiting
La Jolla, California, United States, 92037
Contact: Susan Abel    858-652-5439    abel.susan@scrippshealth.org   
Principal Investigator: Kimberly Harper         
Academic Medical Research Institute, Inc Recruiting
Los Angeles, California, United States, 90022
Contact: Ihsan Hasan    323-725-0051    ihasan@amrionline.net   
Principal Investigator: Mohamed El-Shahawy         
United States, Florida
Outcomes Research International Inc. Recruiting
Hudson, Florida, United States, 34667
Contact: Joann Contino    352-684-8302    jsweetcoordinator@yahoo.com   
Principal Investigator: Muralidhar Acharya         
Jacksonville Center for Clinical Research Recruiting
Jacksonville, Florida, United States, 32216
Contact: Gail Lowe    904-732-6674    ahill@encoredocs.com   
Principal Investigator: Deborah Price         
Coastal Nephrology Associates Research Center Recruiting
Port Charlotte, Florida, United States, 33952
Contact: Beth Jackman    941-258-3556    bjack302@gmail.com   
Principal Investigator: Kianoosh Kaveh         
United States, Kansas
Kansas Nephrology Research Institute Recruiting
Wichita, Kansas, United States, 67214
Contact: Angela Anderson    316-262-2045    aanderson@researchmgmt.com   
Principal Investigator: Dennis Ross         
United States, Maryland
A.Kaldun Nossuli MD/Research Recruiting
Greenbelt, Maryland, United States, 20770
Contact: Alla Levin    301-787-3534    allalevin05@gmail.com   
Principal Investigator: Kaldun Nossuli         
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Elise Hoover    617-636-5941    rperrone@tuftsmedicalcenter.org   
Principal Investigator: Ronald Perrone         
United States, Michigan
Renaissance Renal Research Institute, LLC Recruiting
Detroit, Michigan, United States, 48236
Contact: Rosmarie Henschel    313-432-6271    rhenschel@scsp.net   
Principal Investigator: Keith Bellovich         
Nephrology Center Recruiting
Kalamazoo, Michigan, United States, 49007
Contact: Jean Minger    269-384-5618 ext 218    jean.k.minger@fmc-na.com   
Principal Investigator: Than Oo         
Michigan Kidney Consultants, PC Recruiting
Pontiac, Michigan, United States, 48341
Contact: Joanne Powell    248-253-0330    jpowell@michigankidney.org   
Principal Investigator: Fahd Al-Saghir         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Troy Ofstie    507-255-1087    ofstie.troy@mayo.edu   
Principal Investigator: Vicente Torres         
United States, Nevada
Sierra Nevada Nephrology Recruiting
Reno, Nevada, United States, 89511
Contact: Brady Cartwright    775-322-4550    bcartwright@nevadakidney.com   
Principal Investigator: James Sullivan         
United States, New York
The Rogosin Institute Recruiting
New York, New York, United States, 10021
Contact: Ines Chiccos    212-746-3541    inc9012@nyp.org   
Principal Investigator: Jon Blumenfeld         
United States, North Carolina
University of North Carolina at Chapel Hill - Department of Family Medicine Recruiting
Chapel Hill, North Carolina, United States, 27599-7155
Contact: Anne Froment    919-445-2622    anne_froment@med.unc.edu   
Principal Investigator: Patrick Nachman         
Brookview Hills Research Assoc,LLC Recruiting
Winston Salem, North Carolina, United States, 27103
Contact: Cindy Vanhoy    336-245-6320    cvanhoy@triadbiz.rr.com   
Principal Investigator: James Dilley         
United States, Oregon
Northwest Renal Clinic, Inc. Recruiting
Portland, Oregon, United States, 98686
Contact: Jerimi Boston    503-229-7976    jboston@nwrc.com   
Principal Investigator: Leslie Steed         
United States, Texas
South Arlington Dialysis Center Recruiting
Arlington, Texas, United States, 76015
Contact: Sherali Humeira    817-557-0099    bhskrmehta@yahoo.com   
Principal Investigator: Bhasker R. Mehta         
KidneyAssociates, PLLC Recruiting
Houston, Texas, United States, 77030
Contact: Nikita Dickson    713-795-5511    ndickson@kidneyassociates.com   
Principal Investigator: Stephen Fadem         
United States, Virginia
IntegraTrials, L.L.C. Recruiting
Arlington, Virginia, United States, 22205
Contact: Deborah Tominack    703-528-0385    trialsva@erols.com   
Principal Investigator: Renuka Sothinathan         
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Olga Sergeyeva, MD, MPH Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02160145     History of Changes
Other Study ID Numbers: 156-13-210
Study First Received: June 6, 2014
Last Updated: August 21, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Committee of Ethics in Research
Canada: Health Canada
Czech Republic: State Institute for Drug Control
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Paul-Ehrlich-Institut
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Norway:National Committee for Medical and Health Research Ethics
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Authority for Scientific Research
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Polycystic Kidney Diseases
Multicystic Dysplastic Kidney
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Renal Insufficiency
Kidney Diseases, Cystic
Urogenital Abnormalities
Congenital Abnormalities

ClinicalTrials.gov processed this record on September 22, 2014