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

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ClinicalTrials.gov Identifier: NCT00414440
Recruitment Status : Completed
First Posted : December 21, 2006
Results First Posted : January 14, 2015
Last Update Posted : January 14, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Autosomal Dominant Polycystic Kidney Disease Drug: Placebo Drug: Everolimus Phase 4

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 431 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Study Start Date : December 2006
Actual Primary Completion Date : October 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Everolimus

Arms and Interventions
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Arm Intervention/treatment
Experimental: Everolimus
Patients 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.]).
 Drug: Everolimus
experimental
Other Name: certican
Placebo Comparator: Placebo
Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
 Drug: Placebo
placebo comparator


Outcome Measures
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Primary Outcome Measures :
  1. Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation) [ Time Frame: Baseline, Month 24 ]
    Everolimus (RAD001) compared to placebo with respect to the change from baseline in total kidney volume at Month 24.


Secondary Outcome Measures :
  1. Course of Calculated GFR (mL/Min/1.73 m^2) From Month 24 to Month 60 [ Time Frame: Months 24, 36, 48 and 60 ]
    Course of calculated GFR (mL/min/1.73 m^2) at Months 24, 36, 48 and 60

  2. Calculated GFR, Change From Baseline at Month 60 by Baseline cGFR [ Time Frame: Months 24, 36, 48 and 60 ]
    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.

  3. Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Baseline, Months 12 and 24 ]
    Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), at baseline and then months 12 and 24

  4. Calculated GFR (mL/Min/1.73 m^2), Change From Baseline by Visit [ Time Frame: Months 3, 6, 9, 12, 18 and 24 ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Clinical diagnosis of autosomal dominant polycystic kidney disease ADPKD
  2. Chronic kidney disease (CKD) stage II / III
  3. 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

Exclusion Criteria

  1. ADPKD patients with normal renal function
  2. ADPKD patients with CKD stage IV
  3. Patients with a history of subarachnoid bleeding
  4. Patients with a history of severe infections
  5. Patients with life-threatening urinary tract or cyst infection in the past
  6. Patients who have received any investigational drug within four weeks prior to baseline
  7. 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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00414440


Locations
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Austria
Novartis Investigative Site
Innsbruck, Austria, INNSBRUCK
Novartis Investigative Site
Linz, Austria, A-4010
Novartis Investigative Site
Wien, Austria, 1090
France
Novartis Investigative Site
Brest, France, 29200
Novartis Investigative Site
Grenoble, France, 38043
Novartis Investigative Site
Nantes Cedex, France, 44035
Novartis Investigative Site
Paris cedex 15, France, 75015
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Germany
Novartis Investigative Site
Berlin, Germany, 10117
Novartis Investigative Site
Berlin, Germany, 13353
Novartis Investigative Site
Erlangen, Germany, 91054
Novartis Investigative Site
Essen, Germany, 45147
Novartis Investigative Site
Frankfurt am Main, Germany, 60596
Novartis Investigative Site
Freiburg, Germany, 79106
Novartis Investigative Site
Hamburg, Germany, 20246
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Homburg, Germany, 66421
Novartis Investigative Site
Kiel, Germany, 24105
Novartis Investigative Site
Koeln, Germany, 51109
Novartis Investigative Site
Leipzig, Germany, 04103
Novartis Investigative Site
Lübeck, Germany, 23538
Novartis Investigative Site
Muenster, Germany, 48149
Novartis Investigative Site
Regensburg, Germany, 93053
Novartis Investigative Site
Würzburg, Germany, 97080
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00414440    
Other Study ID Numbers: CRAD001ADE12
2006-001485-16
First Posted: December 21, 2006    Key Record Dates
Results First Posted: January 14, 2015
Last Update Posted: January 14, 2015
Last Verified: January 2015
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
end-stage renal disease, ESRD, autosomal dominant polycystic kidney disease, ADPKD, everolimus
Additional relevant MeSH terms:
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Arthrogryposis
Kidney Diseases
Kidney Failure, Chronic
Polycystic Kidney Diseases
Polycystic Kidney, Autosomal Dominant
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Joint Diseases
Musculoskeletal Diseases
Muscular Diseases
 Musculoskeletal Abnormalities
Congenital Abnormalities
Kidney Diseases, Cystic
Abnormalities, Multiple
Ciliopathies
Genetic Diseases, Inborn
Everolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs