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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 has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02160145
First Posted: June 10, 2014
Last Update Posted: October 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
  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
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

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 ]

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 ]
  • Plasma tolvaptan and metabolites, including DM-4103 plasma concentrations [ Time Frame: Day -1 through Month 15 1/2 ]
  • Uosm and urine specific gravity [ Time Frame: Day -1 through Month 15 1/2 ]

Enrollment: 1370
Study Start Date: May 2014
Study Completion Date: April 14, 2017
Primary Completion Date: April 14, 2017 (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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (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 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
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


  Show 231 Study Locations
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Olga Sergeyeva, MD, MPH Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT02160145     History of Changes
Other Study ID Numbers: 156-13-210
First Submitted: June 6, 2014
First Posted: June 10, 2014
Last Update Posted: October 17, 2017
Last Verified: October 2017

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