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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 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: November 17, 2014
Last verified: November 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

  Show 47 Study Locations
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: November 17, 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
Multicystic Dysplastic Kidney
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Renal Insufficiency, Chronic
Congenital Abnormalities
Kidney Diseases, Cystic
Renal Insufficiency
Urogenital Abnormalities
Urologic Diseases

ClinicalTrials.gov processed this record on November 20, 2014