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
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|ClinicalTrials.gov Identifier: NCT02160145|
Recruitment Status : Completed
First Posted : June 10, 2014
Results First Posted : August 8, 2018
Last Update Posted : August 8, 2018
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|Condition or disease||Intervention/treatment||Phase|
|Chronic Kidney Disease Autosomal Dominant Polycystic Kidney Disease||Drug: Tolvaptan (OPC-41061) Drug: Placebo||Phase 3|
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 (Clinical Trial)|
|Actual Enrollment :||1370 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Study Start Date :||May 2014|
|Actual Primary Completion Date :||April 18, 2017|
|Actual Study Completion Date :||April 18, 2017|
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 Mean Annualized Change in eGFR From Pretreatment Baseline to Post-treatment Follow-up. [ Time Frame: Pretreatment baseline to post-treatment follow-up (up to 61 weeks). ]
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.
- Mean Annualized Slope of eGFR Change [ Time Frame: Pretreatment baseline to post-treatment follow-up (up to 61 weeks). ]
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.
- Mean Change From Baseline in Urine Osmolality During the Double-blind Treatment Period and Post-treatment Follow-up [ Time Frame: Baseline and Months 3, 6, 9 and 12 (End of treatment visit) of the double-blind treatment period, and post-treatment follow-up. ]The mean change from baseline in urine osmolality for the double-blind treatment period collection timepoints and post-treatment follow-up are presented. Baseline was defined as the last evaluation prior to post-randomization dosing.
- Mean Change From Baseline in Urine Specific Gravity During the Double-blind Treatment Period and Post-treatment Follow-up [ Time Frame: Baseline and Months 3, 6, 9 and 12 (End of treatment visit) of the double-blind treatment period, and post-treatment follow-up. ]The mean change from baseline in urine specific gravity for the double-blind treatment period collection timepoints and post-treatment follow up are presented. Baseline was defined as the last evaluation prior to post-randomization dosing.
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|Ages Eligible for Study:||18 Years to 65 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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 Investigational medicinal product (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
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
Documents provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
|Responsible Party:||Otsuka Pharmaceutical Development & Commercialization, Inc.|
|Other Study ID Numbers:||
|First Posted:||June 10, 2014 Key Record Dates|
|Results First Posted:||August 8, 2018|
|Last Update Posted:||August 8, 2018|
|Last Verified:||July 2018|
Chronic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease
Renal Insufficiency, Chronic
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Male Urogenital Diseases
Kidney Diseases, Cystic
Genetic Diseases, Inborn
Antidiuretic Hormone Receptor Antagonists
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs