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

Autosomal Dominant Polycystic Kidney Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00414440
• Other study ID #: CRAD001ADE12
• Secondary ID: 2006-001485-16
• Status: Completed
• Phase: Phase 4
• First received: December 20, 2006
• Last updated: January 13, 2015
• Start date: December 2006
• Est. completion date: October 2013

Study information

• Verified date: January 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Bundesinstitut für Arzneimittel und Medizinproduke
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 431
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autosomal Dominant Polycystic Kidney Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Polycystic Kidney Diseases
• Polycystic Kidney, Autosomal Dominant

Intervention

Drug:
• Placebo
placebo comparator
• Everolimus
experimental

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Innsbruck
Austria	Novartis Investigative Site	Linz
Austria	Novartis Investigative Site	Wien
France	Novartis Investigative Site	Brest
France	Novartis Investigative Site	Grenoble
France	Novartis Investigative Site	Nantes Cedex
France	Novartis Investigative Site	Paris cedex 15
France	Novartis Investigative Site	Toulouse Cedex 4
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt am Main
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Kiel
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lübeck
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Regensburg
Germany	Novartis Investigative Site	Würzburg

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Austria,  France,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Month 24	No
Secondary	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	Months 24, 36, 48 and 60	No
Secondary	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.	Months 24, 36, 48 and 60	No
Secondary	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	Baseline, Months 12 and 24	No
Secondary	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.	Months 3, 6, 9, 12, 18 and 24	No

External Links

•   Link