Back to resultsEfficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
Primary Purpose
Autosomal Dominant Polycystic Kidney Disease
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Placebo
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Autosomal Dominant Polycystic Kidney Disease focused on measuring end-stage renal disease, ESRD, autosomal dominant polycystic kidney disease, ADPKD, everolimus
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Everolimus
Placebo
Arm Description
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.]).
Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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
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.
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
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.
Full Information
NCT ID
NCT00414440
First Posted
December 20, 2006
Last Updated
January 13, 2015
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00414440
Brief Title
Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
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 Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
December 2006 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
October 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autosomal Dominant Polycystic Kidney Disease
Keywords
end-stage renal disease, ESRD, autosomal dominant polycystic kidney disease, ADPKD, everolimus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
431 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Everolimus
Arm Type
Experimental
Arm Description
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.]).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
placebo comparator
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
certican
Intervention Description
experimental
Primary Outcome Measure Information:
Title
Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation)
Description
Everolimus (RAD001) compared to placebo with respect to the change from baseline in total kidney volume at Month 24.
Time Frame
Baseline, Month 24
Secondary Outcome Measure Information:
Title
Course of Calculated GFR (mL/Min/1.73 m^2) From Month 24 to Month 60
Description
Course of calculated GFR (mL/min/1.73 m^2) at Months 24, 36, 48 and 60
Time Frame
Months 24, 36, 48 and 60
Title
Calculated GFR, Change From Baseline at Month 60 by Baseline cGFR
Description
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.
Time Frame
Months 24, 36, 48 and 60
Title
Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description
Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP), at baseline and then months 12 and 24
Time Frame
Baseline, Months 12 and 24
Title
Calculated GFR (mL/Min/1.73 m^2), Change From Baseline by Visit
Description
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.
Time Frame
Months 3, 6, 9, 12, 18 and 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
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
Exclusion Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Innsbruck
ZIP/Postal Code
INNSBRUCK
Country
Austria
Facility Name
Novartis Investigative Site
City
Linz
ZIP/Postal Code
A-4010
Country
Austria
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Brest
ZIP/Postal Code
29200
Country
France
Facility Name
Novartis Investigative Site
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Novartis Investigative Site
City
Nantes Cedex
ZIP/Postal Code
44035
Country
France
Facility Name
Novartis Investigative Site
City
Paris cedex 15
ZIP/Postal Code
75015
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse Cedex 4
ZIP/Postal Code
31054
Country
France
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
10117
Country
Germany
Facility Name
Novartis Investigative Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Novartis Investigative Site
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt am Main
ZIP/Postal Code
60596
Country
Germany
Facility Name
Novartis Investigative Site
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Novartis Investigative Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Novartis Investigative Site
City
Homburg
ZIP/Postal Code
66421
Country
Germany
Facility Name
Novartis Investigative Site
City
Kiel
ZIP/Postal Code
24105
Country
Germany
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
51109
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Lübeck
ZIP/Postal Code
23538
Country
Germany
Facility Name
Novartis Investigative Site
City
Muenster
ZIP/Postal Code
48149
Country
Germany
Facility Name
Novartis Investigative Site
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Novartis Investigative Site
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
20581392
Citation
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. Erratum In: N Engl J Med. 2010 Nov 11;363(20):1977. N Engl J Med. 2010 Sep 16;363(12):1190.
Results Reference
derived
Learn more about this trial
Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
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