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)
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 annualized 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 compare 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 compare the overall and hepatic safety profile of tolvaptan with placebo and to compare incidence of ADPKD complications (outcomes) during the trial
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,370
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.
Matching placebo tablets will be self-administered orally as split-dose regimens, once upon awakening and another approximately 8 to 9 hours later
The Mean Annualized Change in eGFR From Pretreatment Baseline to Post-treatment Follow-up.
The mean annualized change in eGFR was calculated using the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula from pretreatment baseline to post-treatment follow-up, annualized (divided) by each subject's trial duration. The baseline for the primary endpoint was defined as the average of up to 3 eGFR values observed during the screening and placebo run-in periods.
Time frame: Pretreatment baseline to post-treatment follow-up (up to 61 weeks).
Mean Annualized Slope of eGFR Change
To compare the efficacy of tolvaptan treatment in reducing the decline of annualized eGFR slope, as compared with placebo, in subjects with late-stage CKD due to ADPKD who tolerated tolvaptan during an initial run-in period, the annualized rate of eGFR change was derived from each individual subject's eGFR slope using the CKD-EPI formula. The annualized eGFR change slope was derived from all eGFR observations from placebo-run-in, tolvaptan run-in, double-blind treatment and post-treatment follow-up periods using the linear mixed model of analysis. The mean annualized slope of eGFR change is presented.
Time frame: Pretreatment baseline to post-treatment follow-up (up to 61 weeks).
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Birmingham, Alabama, United States
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Huntsville, Alabama, United States
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Mobile, Alabama, United States
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Phoenix, Arizona, United States
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Tempe, Arizona, United States
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Tucson, Arizona, United States
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La Jolla, California, United States
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Los Angeles, California, United States
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Los Angeles, California, United States
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San Francisco, California, United States
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