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Autosomal Dominant Polycystic Kidney Disease (ADPKD)Phase 3TEMPO 4/4NCT01214421

Tolvaptan Extension Study in Participants With ADPKD

A Phase 3 study testing Tolvaptan in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 97 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Tolvaptan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,083 participants
Where
97 sitesin 13 countries
Study dates
26 May 2010to 29 Feb 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)].

Who cannot join

  • 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).
Show all 17Show fewer
  • 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).

Trial locations and contacts

97 sites in 13 countries.

97 sites in 13 countries

United States38 sites

  • Otsuka Investigational Site

    Anderson, South Carolina, 29621

  • Otsuka Investigational Site

    Arlington, Texas, 76015

  • Otsuka Investigational Site

    Atlanta, Georgia, 30322

  • Otsuka Investigational Site

    Augusta, Georgia, 30909

  • Otsuka Investigational Site

    Aurora, Colorado, 80045

  • Otsuka Investigational Site

    Baltimore, Maryland, 21205

  • Otsuka Investigational Site

    Baton Rouge, Louisiana, 70808

  • Otsuka Investigational Site

    Bethlehem, Pennsylvania, 18017

  • Otsuka Investigational Site

    Boston, Massachusetts, 02111

  • Otsuka Investigational Site

    Buffalo, New York, 14215

  • Otsuka Investigational Site

    Chapel Hill, North Carolina, 27599

  • Otsuka Investigational Site

    Charlottesville, Virginia, 22908

  • Otsuka Investigational Site

    Chicago, Illinois, 60611

  • Otsuka Investigational Site

    Cincinnati, Ohio, 45246

  • Otsuka Investigational Site

    Cleveland, Ohio, 44106

  • Otsuka Investigational Site

    Detroit, Michigan, 48236

  • Otsuka Investigational Site

    Hawthorne, New York, 10532

  • Otsuka Investigational Site

    Jacksonville, Florida, 32216

  • Otsuka Investigational Site

    Kansas City, Kansas, 66160

  • Otsuka Investigational Site

    Los Angeles, California, 90025

  • Otsuka Investigational Site

    McAllen, Texas, 78503

  • Otsuka Investigational Site

    Minneapolis, Minnesota, 55404

  • Otsuka Investigational Site

    Mobile, Alabama, 36617

  • Otsuka Investigational Site

    Nashville, Tennessee, 37205

  • Otsuka Investigational Site

    Nashville, Tennessee, 37232

  • Otsuka Investigational Site

    New Haven, Connecticut, 06510

  • Otsuka Investigational Site

    New York, New York, 10021

  • Otsuka Investigational Site

    New York, New York, 10032

  • Otsuka Investigational Site

    Palo Alto, California, 94304

  • Otsuka Investigational Site

    Peoria, Arizona, 85381

  • Otsuka Investigational Site

    Philadelphia, Pennsylvania, 19104

  • Otsuka Investigational Site

    Port Charlotte, Florida, 33952

  • Otsuka Investigational Site

    Portland, Oregon, 97210

  • Otsuka Investigational Site

    Rochester, Minnesota, 55905

  • Otsuka Investigational Site

    Rockville, Maryland, 20850

  • Otsuka Investigational Site

    San Diego, California, 92108

  • Otsuka Investigational Site

    Tempe, Arizona, 85284

  • Otsuka Investigational Site

    Voorhees Township, New Jersey, 08043

Other trials in United States

United Kingdom10 sites

  • Otsuka Investigational Site

    Belfast, BT9 7AB

  • Otsuka Investigational Site

    Birmingham, B15 2TH

  • Otsuka Investigational Site

    Brighton, BN2 5BE

  • Otsuka Investigational Site

    Coventry, CV2 2DX

  • Otsuka Investigational Site

    Edinburgh, EH16 4SA

  • Otsuka Investigational Site

    Inverness, IV2 3UJ

  • Otsuka Investigational Site

    London, NW3 2QG

  • Otsuka Investigational Site

    London, SE5 9RS

  • Otsuka Investigational Site

    London, SW17 0QT

  • Otsuka Investigational Site

    Swansea, SA6 6NL

Other trials in United Kingdom

France7 sites

  • Otsuka Investigational Site

    Bordeaux, 33076

  • Otsuka Investigational Site

    Caen, 14033

  • Otsuka Investigational Site

    Lyon, 69437

  • Otsuka Investigational Site

    Paris, 75018

  • Otsuka Investigational Site

    Reims, 51092

  • Otsuka Investigational Site

    Saint-Etienne, 42055

  • Otsuka Investigational Site

    Toulouse, 31059

Other trials in France

Poland7 sites

  • Otsuka Investigational Site

    Ciechanów, 06-400

  • Otsuka Investigational Site

    Krakow, 31-501

  • Otsuka Investigational Site

    Lodz, 90-153

  • Otsuka Investigational Site

    Lublin, 20-954

  • Otsuka Investigational Site

    Szczecin, 70-111

  • Otsuka Investigational Site

    Warsaw, 04-749

  • Otsuka Investigational Site

    Wroclaw, 50-556

Other trials in Poland

Australia6 sites

  • Otsuka Investigational Site

    Adelaide, South Australia, 5000

  • Otsuka Investigational Site

    Parkville, Victoria, 3050

  • Otsuka Investigational Site

    Perth, Western Australia, 6000

  • Otsuka Investigational Site

    St Leonards, New South Wales, 2065

  • Otsuka Investigational Site

    Westmead, New South Wales, 2145

  • Otsuka Investigational Site

    Woolloongabba, Queensland, 4102

Other trials in Australia

Argentina5 sites

  • Otsuka Investigational Site

    Buenos Aires, C1425APQ

  • Otsuka Investigational Site

    C.a.b.a., Buenos Aires, C1429BWN

  • Otsuka Investigational Site

    Córdoba, 5000

  • Otsuka Investigational Site

    Córdoba, X5016KEH

  • Otsuka Investigational Site

    Pilar, Buenos Aires, B1629ODT

Other trials in Argentina

Germany5 sites

  • Otsuka Investigational Site

    Dresden, 01307

  • Otsuka Investigational Site

    Düsseldorf, 40210

  • Otsuka Investigational Site

    Essen, 45147

  • Otsuka Investigational Site

    Heidelberg, 69120

  • Otsuka Investigational Site

    Nuremberg, 90471

Other trials in Germany

Italy5 sites

  • Otsuka Investigational Site

    Bergamo, 24127

  • Otsuka Investigational Site

    Milan, 20132

  • Otsuka Investigational Site

    Modena, 41100

  • Otsuka Investigational Site

    Naples, 80131

  • Otsuka Investigational Site

    Pavia, 27100

Other trials in Italy

Belgium3 sites

  • Otsuka Investigational Site

    Brussels, 1090

  • Otsuka Investigational Site

    Brussels, 1200

  • Otsuka Investigational Site

    Ghent, 9000

Other trials in Belgium

Canada3 sites

  • Otsuka Investigational Site

    Halifax, Nova Scotia, B3H 1V8

  • Otsuka Investigational Site

    Montreal, Quebec, H3A1A1

  • Otsuka Investigational Site

    Montreal, Quebec, H4J1C5

Other trials in Canada

Romania3 sites

  • Otsuka Investigational Site

    Bucharest, 010731

  • Otsuka Investigational Site

    Bucharest, 022328

  • Otsuka Investigational Site

    Iași, 700504

Other trials in Romania

Russia3 sites

  • Otsuka Investigational Site

    Kemerovo, 650029

  • Otsuka Investigational Site

    Saint Petersburg, 191104

  • Otsuka Investigational Site

    Tomsk, 634063

Other trials in Russia

Netherlands2 sites

  • Otsuka Investigational Site

    Amsterdam, 1081 HV

  • Otsuka Investigational Site

    Groningen, 9713 GZ

Other trials in Netherlands

About this study

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)

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.

Being tested
Tolvaptan
Keywords
Kidney Disease, ADPKD, Autosomal Dominant Polycystic Kidney Disease, Adult Polycystic Kidney Disease
Medical subject headings
Polycystic Kidney, Autosomal Dominant, Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TolvaptanDrug

    Also called OPC-41061, Jinarc

    Tablets of 15 or 30 mg

Study groups in NCT01214421
Study groupRoleWhat they receive
TolvaptanExperimentalParticipants received a daily split-dose of tolvaptan titrated to the maximally tolerated dose, starting daily tolvaptan dose of 45 milligrams (mg) in the morning [AM]/15 mg in the evening [PM] titrated to 60 mg [AM]/30 mg [PM], then 90 mg [AM]/30 mg [PM] based on tolerability were given orally twice daily until the last participant originating from prior studies (either 156-04-251 or 156-04-250, 156-06-260, 156-09-284, 156-09-285, and 156-09-290) who was eligible for efficacy analysis completed the Month 24.
Receives: Drug: Tolvaptan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)

Secondary outcomes (5)

  1. 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]/κ, 1)α × max(Scr/κ, 1)^-1.209 × 0.993 Age × 1.018 (if female) × 1.159 (if black), where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/ĸ or 1, and max indicates the maximum of Scr/κ 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.

    Measured: Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)

  2. 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.

    Measured: Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 in this study (Study 156-08-271)

  3. 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.

    Measured: Study Baseline (Prior to Day 1 in Study 156-08-271) to Month 24 (Study 156-08-271)

  4. 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.

    Measured: Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251

  5. 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.

    Measured: Tolvaptan, Delayed Treated: Baseline to Month 24 in Study 156-08-271; Placebo: Baseline to Month 36 in Study 156-04-251

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2010 (estimated)
  2. Study start26 May 2010
  3. Primary completion29 Feb 2016
  4. Study completion29 Feb 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
1,083 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01214421
Sponsor's protocol ID
156-08-271
Other IDs
2010-018401-10
Acronym
TEMPO 4/4
Status last verified
Sep 2021
First submitted
26 Sep 2010
Last updated
25 Oct 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

Publications

  • Lioudis M, Zhou X, Davenport E, Nunna S, Krasa HB, Oberdhan D, Fernandes AW. Effects of tolvaptan discontinuation in patients with autosomal dominant polycystic kidney disease: a post hoc pooled analysis. BMC Nephrol. 2023 Jun 22;24(1):182. doi: 10.1186/s12882-023-03247-6.

    PubMed 37349694

  • Chebib FT, Zhou X, Garbinsky D, Davenport E, Nunna S, Oberdhan D, Fernandes A. Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies. Kidney Med. 2023 Apr 14;5(6):100639. doi: 10.1016/j.xkme.2023.100639. eCollection 2023 Jun.

    PubMed 37250503

  • Alpers DH, Lewis JH, Hunt CM, Freston JW, Torres VE, Li H, Wang W, Hoke ME, Roth SE, Westcott-Baker L, Estilo A. Clinical Pattern of Tolvaptan-Associated Liver Injury in Trial Participants With Autosomal Dominant Polycystic Kidney Disease (ADPKD): An Analysis of Pivotal Clinical Trials. Am J Kidney Dis. 2023 Mar;81(3):281-293.e1. doi: 10.1053/j.ajkd.2022.08.012. Epub 2022 Sep 30.

    PubMed 36191725

  • 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.

    PubMed 31014270

  • 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.

    PubMed 24470398

  • 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.

    PubMed 21757630

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Tolvaptan in people with Autosomal Dominant Polycystic Kidney Disease (ADPKD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 97 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 97 sites in United States, United Kingdom, France, Poland, Australia and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Oct 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From the Baseline in Total Kidney Volume (TKV) for Study 156-04-251 Participants Enrolled in This Study (156-08-271) (time frame: Study Baseline (Prior to Day 1 in Study 156-04-251) to Month 24 in this study (Study 156-08-271)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01214421, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2021.

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