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

Phase 3

Completed

• Conditions: Autosomal Dominant Polycystic Kidney Disease; Chronic Kidney Disease
• Interventions: Drug: Tolvaptan (OPC-41061); Drug: Placebo

• Registration Number: NCT02160145
• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Brief Summary

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)

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 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 Timeline

• Study Start: 2014-05
• Study First Submitted: 2014-06-06
• Study First Submitted QC: 2014-06-06
• Study First Posted: 2014-06-10
• Primary Completion: 2017-04-18
• Study Completion: 2017-04-18
• Disposition First Submitted: 2017-09-18
• Disposition First Submitted QC: 2017-09-18
• Disposition First Posted: 2017-09-26
• Results First Submitted: 2018-05-01
• Status Verified: 2018-07
• Results First Submitted QC: 2018-07-13
• Last Update Submitted: 2018-07-13
• Results First Posted: 2018-08-08
• Last Update Posted: 2018-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1370

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 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tolvaptan	Tolvaptan (OPC-41061)	Tolvaptan (OPC-41061)
Placebo	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
The Mean Annualized Change in eGFR From Pretreatment Baseline to Post-treatment Follow-up.	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.

Secondary Outcome Measures

Name	Time	Method
Mean Annualized Slope of eGFR Change	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.