Tolvaptan Extension Study in Participants With ADPKD

Autosomal Dominant Polycystic Kidney Disease (ADPKD) Clinical Trial

— TEMPO 4/4  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01214421
• Other study ID #: 156-08-271
• Secondary ID: 2010-018401-10
• Status: Completed
• Phase: Phase 3
• Start date: May 26, 2010
• Est. completion date: February 29, 2016

Study information

• Verified date: September 2021
• Source: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1083
• Est. completion date: February 29, 2016
• Est. primary completion date: February 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Arthrogryposis
• Autosomal Dominant Polycystic Kidney Disease (ADPKD)
• Kidney Diseases
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Tolvaptan
Tablets of 15 or 30 mg

Locations

Country	Name	City	State
Argentina	Otsuka Investigational Site	Buenos Aires
Argentina	Otsuka Investigational Site	C.a.b.a.	Buenos Aires
Argentina	Otsuka Investigational Site	Cordoba
Argentina	Otsuka Investigational Site	Córdoba
Argentina	Otsuka Investigational Site	Pilar	Buenos Aires
Australia	Otsuka Investigational Site	Adelaide	South Australia
Australia	Otsuka Investigational Site	Parkville	Victoria
Australia	Otsuka Investigational Site	Perth	Western Australia
Australia	Otsuka Investigational Site	St. Leonards	New South Wales
Australia	Otsuka Investigational Site	Westmead	New South Wales
Australia	Otsuka Investigational Site	Woolloongabba	Queensland
Belgium	Otsuka Investigational Site	Brussels
Belgium	Otsuka Investigational Site	Brussels
Belgium	Otsuka Investigational Site	Gent
Canada	Otsuka Investigational Site	Halifax	Nova Scotia
Canada	Otsuka Investigational Site	Montreal	Quebec
Canada	Otsuka Investigational Site	Montreal	Quebec
France	Otsuka Investigational Site	Bordeaux
France	Otsuka Investigational Site	Caen Cedex
France	Otsuka Investigational Site	Lyon Cedex 3
France	Otsuka Investigational Site	Paris
France	Otsuka Investigational Site	Reims Cedex
France	Otsuka Investigational Site	Saint-Etienne Cedex 2
France	Otsuka Investigational Site	Toulouse Cedex 09
Germany	Otsuka Investigational Site	Dresden
Germany	Otsuka Investigational Site	Dusseldorf
Germany	Otsuka Investigational Site	Essen
Germany	Otsuka Investigational Site	Heidelberg
Germany	Otsuka Investigational Site	Nurnberg
Italy	Otsuka Investigational Site	Bergamo
Italy	Otsuka Investigational Site	Milano
Italy	Otsuka Investigational Site	Modena
Italy	Otsuka Investigational Site	Napoli
Italy	Otsuka Investigational Site	Pavia
Netherlands	Otsuka Investigational Site	Amsterdam
Netherlands	Otsuka Investigational Site	Groningen
Poland	Otsuka Investigational Site	Ciechanów
Poland	Otsuka Investigational Site	Krakow
Poland	Otsuka Investigational Site	Lodz
Poland	Otsuka Investigational Site	Lublin
Poland	Otsuka Investigational Site	Szczecin
Poland	Otsuka Investigational Site	Warszawa
Poland	Otsuka Investigational Site	Wroclaw
Romania	Otsuka Investigational Site	Bucuresti
Romania	Otsuka Investigational Site	Bucuresti
Romania	Otsuka Investigational Site	Iasi
Russian Federation	Otsuka Investigational Site	Kemerovo
Russian Federation	Otsuka Investigational Site	St. Petersburg
Russian Federation	Otsuka Investigational Site	Tomsk
United Kingdom	Otsuka Investigational Site	Belfast
United Kingdom	Otsuka Investigational Site	Birmingham
United Kingdom	Otsuka Investigational Site	Brighton
United Kingdom	Otsuka Investigational Site	Coventry
United Kingdom	Otsuka Investigational Site	Edinburgh
United Kingdom	Otsuka Investigational Site	Inverness
United Kingdom	Otsuka Investigational Site	London
United Kingdom	Otsuka Investigational Site	London
United Kingdom	Otsuka Investigational Site	London
United Kingdom	Otsuka Investigational Site	Swansea
United States	Otsuka Investigational Site	Anderson	South Carolina
United States	Otsuka Investigational Site	Arlington	Texas
United States	Otsuka Investigational Site	Atlanta	Georgia
United States	Otsuka Investigational Site	Augusta	Georgia
United States	Otsuka Investigational Site	Aurora	Colorado
United States	Otsuka Investigational Site	Baltimore	Maryland
United States	Otsuka Investigational Site	Baton Rouge	Louisiana
United States	Otsuka Investigational Site	Bethlehem	Pennsylvania
United States	Otsuka Investigational Site	Boston	Massachusetts
United States	Otsuka Investigational Site	Buffalo	New York
United States	Otsuka Investigational Site	Chapel Hill	North Carolina
United States	Otsuka Investigational Site	Charlottesville	Virginia
United States	Otsuka Investigational Site	Chicago	Illinois
United States	Otsuka Investigational Site	Cincinnati	Ohio
United States	Otsuka Investigational Site	Cleveland	Ohio
United States	Otsuka Investigational Site	Detroit	Michigan
United States	Otsuka Investigational Site	Hawthorne	New York
United States	Otsuka Investigational Site	Jacksonville	Florida
United States	Otsuka Investigational Site	Kansas City	Kansas
United States	Otsuka Investigational Site	Los Angeles	California
United States	Otsuka Investigational Site	McAllen	Texas
United States	Otsuka Investigational Site	Minneapolis	Minnesota
United States	Otsuka Investigational Site	Mobile	Alabama
United States	Otsuka Investigational Site	Nashville	Tennessee
United States	Otsuka Investigational Site	Nashville	Tennessee
United States	Otsuka Investigational Site	New Haven	Connecticut
United States	Otsuka Investigational Site	New York	New York
United States	Otsuka Investigational Site	New York	New York
United States	Otsuka Investigational Site	Palo Alto	California
United States	Otsuka Investigational Site	Peoria	Arizona
United States	Otsuka Investigational Site	Philadelphia	Pennsylvania
United States	Otsuka Investigational Site	Port Charlotte	Florida
United States	Otsuka Investigational Site	Portland	Oregon
United States	Otsuka Investigational Site	Rochester	Minnesota
United States	Otsuka Investigational Site	Rockville	Maryland
United States	Otsuka Investigational Site	San Diego	California
United States	Otsuka Investigational Site	Tempe	Arizona
United States	Otsuka Investigational Site	Voorhees	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Development & Commercialization, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  France,  Germany,  Italy,  Netherlands,  Poland,  Romania,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271)	Total kidney volume is a measure of disease progression in the ADPKD participants. Kidney volume was assessed in T1-weighted magnetic resonance images collected at each study site and sent to a central reviewing facility. At the central reviewing facility, radiologists used proprietary software to measure the volume of both kidneys in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). The percent change in the volume of both kidneys combined was analysed using mixed-effect model repeated measures (MMRM) analysis and reported. This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.	Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
Secondary	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)	Estimated Glomerular Filtration Rate (eGFR) according to CKD-EPI is calculated using the CKD-EPI equation, expressed as a single equation, is GFR = 141 × min (serum creatinine [Scr]/?, 1)a × max(Scr/?, 1)^-1.209 × 0.993 Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, ? is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/? or 1, and max indicates the maximum of Scr/? or 1 in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in eGFR for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). MMRM was used for the analysis. This outcome measure was analyzed only in the participants enrolled from the previous - 156-04-251, as pre-specified in the protocol.	Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)
Secondary	Annualized Slope of Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in Study 156-08-271	Annualized slope of TKV is a measure of renal function and disease progression in ADPKD participants. The annualized slope is calculated as percentage of growth in TKV (measured in mL by MRI) divided by each participant's years of participation for all participants was calculated using MMRM analysis in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing annualized slope of TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.	Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 in this study (Study 156-08-271)
Secondary	Annualized Slope of eGFR (CKD-EPI) for Study 156-04-251 Participants Enrolled in Study 156-08-271	Annualized slope of eGFR (CKD-EPI) is a measure of renal function and disease progression in ADPKD participants. The annualized slope of eGFR (CKD-EPI) (divided by each participant's years of participation) for all participants was calculated using MMRM analysis in participants continuing from previous study (156-04-251) at Month 24 of this study (156-08-271) comparing change in TKV for the early-treated (those previously treated with tolvaptan) to delayed-treated (those previously treated with placebo). eGFR was calculated using the Chronic Kidney Disease-Epidemiology (CKD-EPI) formula. This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251, as pre-specified in the protocol.	Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 (Study 156-08-271)
Secondary	Annualized TKV Slope for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271	Annualized slope of TKV is a measure of renal function and disease progression in ADPKD participants. The annualized slope is calculated as percentage of growth in TKV (measured in mL by MRI) divided by each participant's years of participation, using MMRM analysis to compare annualized slope of TKV for the participants who received placebo in previous study (156-04-251) to annualized slope of TKV for the same participants who received tolvaptan in this study (156-08-271). This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251 and who received placebo in the previous study, as pre-specified in the protocol.	Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251
Secondary	Annualized Slope of Renal Function (eGFRCKD-EPI) for Study 156-04-251 Placebo Participants Enrolled in Study 156-08-271	Annualized slope of eGFR (CKD-EPI) is a measure of renal function and disease progression in ADPKD participants. The annualized slope of eGFR (calculated using CKD-EPI formula) divided by each participant's years of participation, using MMRM analysis to compare annualized slope of eGFR (CKD-EPI) for the participants who received placebo in previous study (156-04-251) to the annualized slope of eGFR (CKD-EPI) for the same participants who received tolvaptan in this study (156-08-271). This outcome measure was analyzed only in the participants enrolled from the previous study - 156-04-251 who received placebo in previous study and received tolvaptan in this study, as pre-specified in the protocol.	Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251