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
|Chronic Kidney Disease Autosomal Dominant Polycystic Kidney Disease||Drug: Tolvaptan (OPC-41061) Drug: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (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|
- 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 ]
- 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 ]
|Study Start Date:||May 2014|
|Estimated Study Completion Date:||April 2017|
|Estimated Primary Completion Date:||April 2017 (Final data collection date for primary outcome measure)|
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
Matching placebo tablets will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT02160145
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|Study Director:||Olga Sergeyeva, MD, MPH||Otsuka Pharmaceutical Development & Commercialization, Inc.|