AzTrials
AzTrials

Autosomal Dominant Polycystic Kidney DiseasePhase 4NCT00414440

Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease

A Phase 4 study testing Everolimus in people with Autosomal Dominant Polycystic Kidney Disease, run by Novartis Pharmaceuticals at 24 sites in 3 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

This study will assess whether everolimus (RAD001) is effective in preventing cyst and kidney expansion as well as worsening of renal function in patients with ADPKD and whether the application of 5 mg/day everolimus as monotherapy is safe and well tolerated. Read more about this study

Who is it for?
Ages 18 to 50 years
What is being tested?
Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
431 participants
Where
24 sitesin 3 countries
Study dates
Dec 2006to Oct 2013
Phase
Phase 4
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 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Clinical diagnosis of autosomal dominant polycystic kidney disease ADPKD
  • Chronic kidney disease (CKD) stage II / III
  • Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at baseline, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility

Who cannot join

  • ADPKD patients with normal renal function
  • ADPKD patients with CKD stage IV
  • Patients with a history of subarachnoid bleeding
  • Patients with a history of severe infections
  • Patients with life-threatening urinary tract or cyst infection in the past
  • Patients who have received any investigational drug within four weeks prior to baseline
  • Patients who have been treated with any non-protocol immunosuppressive drug or treatment within one month prior to baseline
  • Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

24 sites in 3 countries.

24 sites in 3 countries

Germany16 sites
  • Novartis Investigative Site

    Berlin, 10117

  • Novartis Investigative Site

    Berlin, 13353

  • Novartis Investigative Site

    Cologne, 51109

  • Novartis Investigative Site

    Erlangen, 91054

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    Frankfurt am Main, 60596

  • Novartis Investigative Site

    Freiburg im Breisgau, 79106

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Heidelberg, 69120

  • Novartis Investigative Site

    Homburg, 66421

  • Novartis Investigative Site

    Kiel, 24105

  • Novartis Investigative Site

    Leipzig, 04103

  • Novartis Investigative Site

    Lübeck, 23538

  • Novartis Investigative Site

    Münster, 48149

  • Novartis Investigative Site

    Regensburg, 93053

  • Novartis Investigative Site

    Würzburg, 97080

Other trials in Germany

France5 sites
  • Novartis Investigative Site

    Brest, 29200

  • Novartis Investigative Site

    Grenoble, 38043

  • Novartis Investigative Site

    Nantes, 44035

  • Novartis Investigative Site

    Paris, 75015

  • Novartis Investigative Site

    Toulouse, 31054

Other trials in France

Austria3 sites
  • Novartis Investigative Site

    Innsbruck, INNSBRUCK

  • Novartis Investigative Site

    Linz, A-4010

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

About this study

Official title: A Multicenter, Randomized, Placebo-controlled, Double-blind Study on the Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease (ESRD) in Patients With Autosomal Dominant Polycystic Kidney Disease (ADPKD)

This study will assess whether everolimus (RAD001) is effective in preventing cyst and kidney expansion as well as worsening of renal function in patients with ADPKD and whether the application of 5 mg/day everolimus as monotherapy is safe and well tolerated.

Being tested
Placebo, Everolimus
Keywords
end-stage renal disease, ESRD, autosomal dominant polycystic kidney disease, ADPKD, everolimus
Medical subject headings
Polycystic Kidney, Autosomal Dominant, Kidney Failure, Chronic

What participants receive

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

  • PlaceboDrug

    placebo comparator

  • EverolimusDrug

    Also called certican

    experimental

Study groups in NCT00414440
Study groupRoleWhat they receive
EverolimusExperimentalPatients in the everolimus group initially received 5 mg/day everolimus divided in 2 equal doses (i.e. 2.5 mg b.i.d.). Dose adjustments were performed to achieve a blood trough level of 3-8 ng/mL (maximum daily dose: 10 mg/day [5 mg b.i.d.]).
Receives: Drug: Everolimus
PlaceboPlacebo comparatorPlacebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
Receives: Drug: Placebo

What is being measured

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

  1. Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation)

    Everolimus (RAD001) compared to placebo with respect to the change from baseline in total kidney volume at Month 24.

    Measured: Baseline, Month 24

Secondary outcomes (4)
  1. Course of Calculated GFR (mL/Min/1.73 m^2) From Month 24 to Month 60

    Course of calculated GFR (mL/min/1.73 m^2) at Months 24, 36, 48 and 60

    Measured: Months 24, 36, 48 and 60

  2. Calculated GFR, Change From Baseline at Month 60 by Baseline cGFR

    Change in renal function was assessed by the estimated Glomerular Filtration Rate (eGFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m^2) = 186.3*(C^-1.154)*(A^-0.203)*G*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1. The changes in renal function were analyzed via analysis of covariance (ANCOVA) with treatment, pre-transplant hepatitis C virus status and randomization eGFR as covariates. Based on these ANCOVA analyses, the least-squares mean and standard errors of change were reported.

    Measured: Months 24, 36, 48 and 60

  3. Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), at baseline and then months 12 and 24

    Measured: Baseline, Months 12 and 24

  4. Calculated GFR (mL/Min/1.73 m^2), Change From Baseline by Visit

    Change in renal function was assessed by the Glomerular Filtration Rate (GFR) using the abbreviated (4 variables) Modification of Diet in Renal Disease (MDRD-4) formula which was developed by the MDRD Study Group and has been validated in patients with chronic kidney disease. The MDRD-4 formula used for the eGFR calculation is: eGFR (mL/min/1.73m^2) = 186.3*(C^-1.154)*(A^-0.203)*G*R, where C is the serum concentration of creatinine (mg/dL), A is age (years), G=0.742 when gender is female, otherwise G=1, R=1.21 when race is black, otherwise R=1. The changes in renal function were analyzed via analysis of covariance (ANCOVA) with treatment, pre-transplant hepatitis C virus status and randomization eGFR as covariates. Based on these ANCOVA analyses, the least-squares mean and standard errors of change were reported.

    Measured: Months 3, 6, 9, 12, 18 and 24

Timeline

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

  1. First posted21 Dec 2006 (estimated)
  2. Study startDec 2006
  3. Primary completionOct 2013
  4. Study completionOct 2013

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
431 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00414440
Sponsor's protocol ID
CRAD001ADE12
Other IDs
2006-001485-16
Status last verified
Jan 2015
First submitted
20 Dec 2006
Last updated
14 Jan 2015

Publications

  • St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

    PubMed 39356039
  • Walz G, Budde K, Mannaa M, Nurnberger J, Wanner C, Sommerer C, Kunzendorf U, Banas B, Horl WH, Obermuller N, Arns W, Pavenstadt H, Gaedeke J, Buchert M, May C, Gschaidmeier H, Kramer S, Eckardt KU. Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2010 Aug 26;363(9):830-40. doi: 10.1056/NEJMoa1003491. Epub 2010 Jun 26.

    PubMed 20581392

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Everolimus in people with Autosomal Dominant Polycystic Kidney Disease, run by Novartis Pharmaceuticals at 24 sites in 3 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 3 inclusion and 8 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 14 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Germany, France, Austria. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 14 Jan 2015). 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?

Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation) (time frame: Baseline, Month 24). 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 NCT00414440, which also lists 2 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 14 Jan 2015.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in