Clinical trial NCT01214421: Tolvaptan Extension Study in Participants With ADPKD
Official title: Multi-center, Open-label, Extension Study to Evaluate the Long-term Efficacy and Safety of Oral Tolvaptan Tablet Regimens in Subjects With Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Keywords: Kidney Disease
ADPKD
Autosomal Dominant Polycystic Kidney Disease
Adult Polycystic Kidney Disease
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2010-10-05
Enrollment: 1083
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To demonstrate whether tolvaptan modifies ADPKD progression as measured by changes from Baseline (from Study 156-04-251) in total kidney volume (TKV) and renal function.


Eligibility criteria: Inclusion Criteria:

- Participants who had successfully completed a Phase 1, 2, or 3 tolvaptan ADPKD or renal impairment study, with a confirmed diagnosis of ADPKD from prior studies \[either 156-04-251 (NCT00428948) or 156-04-250 (NCT00413777), 156-06-260, 156-09-284 (NCT01336972), 156-09-285 (NCT01210560), and 156-09-290 (NCT01451827)\].

Exclusion Criteria:

* Participants unable to provide written informed consent.
* Participants (men or women) would not adhere to the reproductive precautions as outlined in the Informed Consent Form.
* Participants (women only) with a positive urine pregnancy test.
* Participants who were pregnant or breast-feeding.
* Participants unable to take oral medications.
* Participants who had allergic reactions to tolvaptan or chemically related structures such as benzazepines (benzazepril, conivaptan, fenoldopam mesylate, or mirtazapine).
* Participants with disorders in thirst recognition or an inability to access fluids.
* Participants with critical electrolyte imbalances, as determined by the investigator
* Participants with or at risk of significant hypovolemia, as determined by investigator.
* Participants with significant anemia, as determined by investigator.
* Participants with a history of substance abuse (within the last 3 years).
* Participants who were taking other experimental (that is, non-marketed) therapies or were participating in another clinical drug or device study; participating in the off-drug follow-up period of another ADPKD trial with tolvaptan was permitted.
* Participants unable to complete magnetic resonance imaging (MRI) assessments (for example, participants with ferro-magnetic prostheses, aneurysm clips, severe claustrophobia).
* Participants who had taken a vasopressin antagonist (outside of previous participation in a tolvaptan study).
* Participants unable to comply with anti-hypertensive or other important medical therapy.
* Participants with advanced diabetes.
* Participants who were taking medications or had an illness that could confound endpoint assessments (including taking approved therapies for the purpose of affecting polycystic kidney disease \[PKD\] cysts).

Primary outcomes:
measure: Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)
timeFrame: Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
Secondary outcomes:
measure: Change From the Baseline in Estimated Glomerular Filtration Rate (eGFR) as Assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)
timeFrame: Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
measure: Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271
timeFrame: Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 in this study (Study 156-08-271)
measure: Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271
timeFrame: Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 (Study 156-08-271)
measure: Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271
timeFrame: Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251
measure: Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271
timeFrame: Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Otsuka Investigational Site
state: Alabama
city: Peoria
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facility: Otsuka Investigational Site
state: Arizona
city: Tempe
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facility: Otsuka Investigational Site
state: Arizona
city: Los Angeles
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city: Palo Alto
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state: California
city: San Diego
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state: Colorado
city: New Haven
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facility: Otsuka Investigational Site
state: Connecticut
city: Jacksonville
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city: Port Charlotte
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facility: Otsuka Investigational Site
state: Florida
city: Atlanta
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state: Georgia
city: Augusta
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facility: Otsuka Investigational Site
state: Georgia
city: Chicago
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facility: Otsuka Investigational Site
state: Illinois
city: Kansas City
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state: Kansas
city: Baton Rouge
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facility: Otsuka Investigational Site
state: Louisiana
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state: Maryland
city: Rockville
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facility: Otsuka Investigational Site
state: Maryland
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state: Massachusetts
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state: Michigan
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city: Pilar
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state: Buenos Aires
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city: Woolloongabba
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city: Adelaide
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state: Quebec
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country: France
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country: France
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country: France
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country: Germany
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city: Dusseldorf
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facility: Otsuka Investigational Site
city: Essen
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city: Heidelberg
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city: Nurnberg
country: Germany
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city: Bergamo
country: Italy
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city: Milano
country: Italy
facility: Otsuka Investigational Site
city: Modena
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facility: Otsuka Investigational Site
city: Napoli
country: Italy
facility: Otsuka Investigational Site
city: Pavia
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city: Amsterdam
country: Netherlands
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city: Groningen
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city: Ciechanów
country: Poland
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city: Krakow
country: Poland
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city: Lodz
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city: Lublin
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city: Szczecin
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country: Poland
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city: Wrocław
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country: Romania
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country: Romania
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country: Russian Federation
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country: Russian Federation
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country: Russian Federation
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city: Belfast
country: United Kingdom
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city: Birmingham
country: United Kingdom
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city: Brighton
country: United Kingdom
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city: Coventry
country: United Kingdom
facility: Otsuka Investigational Site
city: Edinburgh
country: United Kingdom
facility: Otsuka Investigational Site
city: Inverness
country: United Kingdom
facility: Otsuka Investigational Site
city: London
country: United Kingdom
facility: Otsuka Investigational Site
city: London
country: United Kingdom
facility: Otsuka Investigational Site
city: London
country: United Kingdom
facility: Otsuka Investigational Site
city: Swansea
country: United Kingdom
facility: Otsuka Investigational Site
Study officials:
affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.
name: Study Director
role: STUDY_DIRECTOR
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: Thimmappa ND, Blumenfeld JD, Cerilles MA, Dunning A, Donahue SL, Bobb WO, Zhang HL, Prince MR. Cisterna chyli in autosomal dominant polycystic kidney disease. J Magn Reson Imaging. 2015 Jan;41(1):142-8. doi: 10.1002/jmri.24527. Epub 2014 Jan 27.
citation: Blumenfeld JD, Tepler J, Mauer A, Coller B, Bichet DG, Smith B. Tolvaptan inhibition of desmopressin effects on coagulation factors in a patient with decreased von Willebrand factor and polycystic kidney disease. Blood. 2011 Jul 14;118(2):474-6. doi: 10.1182/blood-2011-04-347328. No abstract available.