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

Novartis Pharmaceuticals431 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

431

Conditions

Autosomal Dominant Polycystic Kidney Disease

Interventions

PlaceboDRUG

placebo comparator

EverolimusDRUG

experimental

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 Years

Medical Language ↔ Plain English

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

Locations (24)

Novartis Investigative Site

Innsbruck, Austria

Outcomes

Primary Outcomes

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.

Time frame: Baseline, Month 24

Secondary Outcomes

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

Time frame: 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.

Time frame: Months 24, 36, 48 and 60

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

Time frame: Baseline, 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.

Data from ClinicalTrials.gov

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