Efficacy, Safety and Tolerability of Everolimus in Preventing End-stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease
- Conditions
- Autosomal Dominant Polycystic Kidney Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT00414440
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 431
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Everolimus 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 \[5 mg b.i.d.\]). Placebo Placebo Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.
- Primary Outcome Measures
Name Time Method Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation) 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
Name Time Method Course of Calculated GFR (mL/Min/1.73 m^2) From Month 24 to Month 60 Months 24, 36, 48 and 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 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.
Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Baseline, Months 12 and 24 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 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.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇩🇪Würzburg, Germany