Clinical trial NCT02160145: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease
Keywords: Chronic Kidney Disease
Autosomal Dominant Polycystic Kidney Disease
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2014-06-10
Enrollment: 1370
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility 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 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

Primary outcomes:
measure: The Mean Annualized Change in eGFR From Pretreatment Baseline to Post-treatment Follow-up.
timeFrame: Pretreatment baseline to post-treatment follow-up (up to 61 weeks).
Secondary outcomes:
measure: Mean Annualized Slope of eGFR Change
timeFrame: Pretreatment baseline to post-treatment follow-up (up to 61 weeks).
Other outcomes:
measure: Mean Change From Baseline in Urine Osmolality During the Double-blind Treatment Period and Post-treatment Follow-up
timeFrame: Baseline and Months 3, 6, 9 and 12 (End of treatment visit) of the double-blind treatment period, and post-treatment follow-up.
measure: Mean Change From Baseline in Urine Specific Gravity During the Double-blind Treatment Period and Post-treatment Follow-up
timeFrame: Baseline and Months 3, 6, 9 and 12 (End of treatment visit) of the double-blind treatment period, and post-treatment follow-up.
Locations:
city: Birmingham
country: United States
state: Alabama
city: Huntsville
country: United States
state: Alabama
city: Mobile
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Tempe
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: La Jolla
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state: California
city: Los Angeles
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state: California
city: Los Angeles
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state: California
city: San Francisco
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state: California
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state: Colorado
city: Denver
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city: New Haven
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state: Connecticut
city: Hudson
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city: Lyon Cedex 03
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country: Romania
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country: Romania
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country: Russian Federation
city: St. Petersburg
country: Russian Federation
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country: Russian Federation
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country: Russian Federation
city: Pretoria
country: South Africa
state: Gauteng
city: Durban
country: South Africa
state: KwaZulu-Natal
city: Cape Town
country: South Africa
state: Western Cape
city: L'Hospitalet de Llobregat
country: Spain
state: Barcelona
city: Ciudad Real
country: Spain
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country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
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country: Spain
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country: Spain
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country: Sweden
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country: Sweden
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country: Sweden
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city: Salford
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city: Inverness
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state: Highland Region
city: Leicester
country: United Kingdom
state: Leicestershire
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city: Liverpool
country: United Kingdom
state: Merseyside
city: Middlesbrough
country: United Kingdom
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city: Sheffield
country: United Kingdom
state: South Yorkshire
city: Stoke-on-Trent
country: United Kingdom
state: Staffordshire
city: Newcastle upon Tyne
country: United Kingdom
state: Tyne & Wear
city: Coventry
country: United Kingdom
state: Warwickshire
city: Swansea
country: United Kingdom
Study officials:
References:
citation: Bennett H, McEwan P, Hamilton K, O'Reilly K. Modelling the long-term benefits of tolvaptan therapy on renal function decline in autosomal dominant polycystic kidney disease: an exploratory analysis using the ADPKD outcomes model. BMC Nephrol. 2019 Apr 23;20(1):136. doi: 10.1186/s12882-019-1290-5.
citation: Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Perrone RD, Koch G, Ouyang J, McQuade RD, Blais JD, Czerwiec FS, Sergeyeva O; REPRISE Trial Investigators. Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease. N Engl J Med. 2017 Nov 16;377(20):1930-1942. doi: 10.1056/NEJMoa1710030. Epub 2017 Nov 4.