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CompletedNCT00414440Updated Jan 14, 2015Results posted

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

A Phase 4 interventional study of Placebo and Everolimus in Autosomal Dominant Polycystic Kidney Disease, sponsored by Novartis Pharmaceuticals. Completed at 24 sites in 3 countries. Open to participants aged 18 Years to 50 Years. Per ClinicalTrials.gov, last updated 2015-01-14.

Sponsored by Novartis Pharmaceuticals · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
431
Allocation
Randomized
Ages
18 Years to 50 Years
Sex
All
01

Study 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.

02

Conditions studied

  • Autosomal Dominant Polycystic Kidney Disease

Keywords

  • end-stage renal disease, ESRD, autosomal dominant polycystic kidney disease, ADPKD, everolimus
03

In context

Arthrogryposis

85 studies on the registry are indexed under Arthrogryposis; 10 are open to participants now.

This study's enrollment of 431 is above the median of 66 across 63 interventional studies indexed under Arthrogryposis.

Browse Arthrogryposis studies →

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.

Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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

05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
431 participants (actual)

Study arms

  • 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

  • Placebo comparator
    Placebo

    Placebo tablets equivalent to the dosage of everolimus 5 mg/day, divided in 2 equal doses.

    Drug: Placebo

Interventions

  • DrugPlacebo

    placebo comparator

  • DrugEverolimus

    experimental

    Also known as: certican

06

What researchers measure

Primary outcomes

  1. 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

  1. 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

  2. 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

  3. 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

  4. 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.

    Time frame: Months 3, 6, 9, 12, 18 and 24

07

Results

Posted Jan 14, 2015

Participant flow

Core Period
Participant flow — Core Period
MilestoneEverolimusPlacebo
Started214217
Completed144185
Not completed7032
Withdrew: Withdrawal by subject7032
Extension Period
Participant flow — Extension Period
MilestoneEverolimusPlacebo
Started214217
Completed6477
Not completed150140
Withdrew: Lost to follow-up4452
Withdrew: Did not consent to continue follow up6154
Withdrew: Other11
Withdrew: Administrative1616
Withdrew: Death12
Withdrew: Withdrawal by subject97
Withdrew: Not included in follow up period188

Outcome measures

PrimaryPrimary 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
Reported as:
Mean · mL
Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation)
mLEverolimusPlacebo
Primary Efficacy Analysis of Total Kidney Volume (mITT Set, Multiple Imputation)230.1 (172.4 to 287.9)300.8 (247.5 to 354.1)
SecondaryCourse 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
Reported as:
Mean · mL/min/1.73 m^2
Course of Calculated GFR (mL/Min/1.73 m^2) From Month 24 to Month 60
mL/min/1.73 m^2EverolimusPlacebo
Month 2443.9 ± 23.948.8 ± 20.8
Month 3642.6 ± 23.544.9 ± 22.2
Month 4839.6 ± 22.242.7 ± 22.5
Month 6037.7 ± 23.837.6 ± 21.6
SecondaryCalculated 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
Reported as:
Mean · mL/min/1.73 m^2
Calculated GFR, Change From Baseline at Month 60 by Baseline cGFR
mL/min/1.73 m^2EverolimusPlacebo
>70 mL/min/1.73 m^2 n=11, 18-14.8 ± 22.7-20.5 ± 11.1
≤70 mL/min/1.73 m^2 n=53, 57-16.1 ± 17.6-15.6 ± 15.2
>60 mL/min/1.73 m^2 n=21.26-17.0 ± 17.3-20.0 ± 13.6
≤60 mL/min/1.73 m^2 n=43,49-15.3 ± 19.0-15.1 ± 14.7
>50 mL/min/1.73 m^2 n=36,39-19.0 ± 17.3-19.4 ± 12.6
≤50 mL/min/1.73 m^2 n=28, 36-11.8 ± 19.2-14.0 ± 15.8
SecondaryChanges 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
Reported as:
Mean · mmHG
Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
mmHGEverolimusPlacebo
Baseline SBP136 ± 16135 ± 17
Month 12 SBP134 ± 15134 ± 16
Month 24 SBP134 ± 17134 ± 15
Baseline DBP88 ± 1188 ± 10
Month 12 DBP86 ± 1086 ± 10
Month 24 DBP85 ± 1085 ± 10
SecondaryCalculated 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.

Time frame:
Months 3, 6, 9, 12, 18 and 24
Reported as:
Mean · mL/min/1.73m^2
Calculated GFR (mL/Min/1.73 m^2), Change From Baseline by Visit
mL/min/1.73m^2EverolimusPlacebo
Week 12.0 ± 5.9-0.9 ± 6.1
Week 21.7 ± 5.9-0.9 ± 6.5
Week 40.6 ± 6.3-1.2 ± 6.7
Month 3-0.5 ± 8.2-2.4 ± 6.7
Month 6-2.3 ± 7.7-2.2 ± 6.7
Month 9-4.6 ± 8.2-2.4 ± 6.0
Month 12-5.4 ± 7.5-3.2 ± 6.9
Month 18-7.7 ± 8.5-5.5 ± 6.7
Month 24-8.9 ± 8.8-7.7 ± 6.6

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Everolimus—80/214 (37.4%)205/214 (95.8%)
Placebo—51/217 (23.5%)185/217 (85.3%)
Most frequent serious events
Showing 10 of 185
Most frequent serious events
EventEverolimusPlacebo
ANGIOEDEMASkin and subcutaneous tissue disorders8/2140/217
OVARIAN CYSTReproductive system and breast disorders7/2140/217
PNEUMONIAInfections and infestations5/2141/217
RENAL FAILURE ACUTERenal and urinary disorders5/2141/217
DISEASE PROGRESSIONGeneral disorders4/2142/217
WEIGHT DECREASEDInvestigations4/2140/217
MYALGIAMusculoskeletal and connective tissue disorders4/2141/217
INGUINAL HERNIAGastrointestinal disorders2/2144/217
RENAL CYST INFECTIONInfections and infestations2/2144/217
DIARRHOEAGastrointestinal disorders3/2141/217
Most frequent other events
Showing 10 of 41
Most frequent other events
EventEverolimusPlacebo
APHTHOUS STOMATITISGastrointestinal disorders83/21412/217
NASOPHARYNGITISInfections and infestations83/21483/217
DIARRHOEAGastrointestinal disorders48/21434/217
HYPERCHOLESTEROLAEMIAMetabolism and nutrition disorders46/2148/217
OEDEMA PERIPHERALGeneral disorders42/21420/217
LEUKOPENIABlood and lymphatic system disorders38/2146/217
BLOOD CREATININE INCREASEDInvestigations38/21413/217
HEADACHENervous system disorders37/21427/217
ANAEMIABlood and lymphatic system disorders35/21411/217
HYPERTENSIONVascular disorders33/21429/217

Baseline characteristics

Age, Continuous
Age, Continuous(years)EverolimusPlaceboTotal
Mean44.6 ± 10.144.5 ± 10.444.5 ± 10.3
Sex: Female, Male
Sex: Female, Male(Participants)EverolimusPlaceboTotal
Female105117222
Male109100209
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)EverolimusPlaceboTotal
Asian Oriental404
Black or African American101
White208217425
Other, Unknown or Not Reported101
08

Study locations

24 sites
  • Novartis Investigative Site
    Innsbruck, INNSBRUCK, Austria
  • Novartis Investigative Site
    Linz, A-4010, Austria
  • Novartis Investigative Site
    Wien, 1090, Austria
  • Novartis Investigative Site
    Brest, 29200, France
  • Novartis Investigative Site
    Grenoble, 38043, France
  • Novartis Investigative Site
    Nantes Cedex, 44035, France
  • Novartis Investigative Site
    Paris cedex 15, 75015, France
  • Novartis Investigative Site
    Toulouse Cedex 4, 31054, France
  • Novartis Investigative Site
    Berlin, 10117, Germany
  • Novartis Investigative Site
    Berlin, 13353, Germany
  • Novartis Investigative Site
    Erlangen, 91054, Germany
  • Novartis Investigative Site
    Essen, 45147, Germany
  • Novartis Investigative Site
    Frankfurt am Main, 60596, Germany
  • Novartis Investigative Site
    Freiburg, 79106, Germany
  • Novartis Investigative Site
    Hamburg, 20246, Germany
  • Novartis Investigative Site
    Heidelberg, 69120, Germany
  • Novartis Investigative Site
    Homburg, 66421, Germany
  • Novartis Investigative Site
    Kiel, 24105, Germany
  • Novartis Investigative Site
    Koeln, 51109, Germany
  • Novartis Investigative Site
    Leipzig, 04103, Germany
  • Novartis Investigative Site
    Lübeck, 23538, Germany
  • Novartis Investigative Site
    Muenster, 48149, Germany
  • Novartis Investigative Site
    Regensburg, 93053, Germany
  • Novartis Investigative Site
    Würzburg, 97080, Germany
09

References and documents

Publications

  • 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. PubMed 20581392 ↗

Related links

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jan 14, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00414440
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Dec 21, 2006
Start date
Dec 2006
Primary completion
Oct 2013
Completion
Oct 2013
Results posted
Jan 14, 2015
Last update
Jan 14, 2015

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals
View the source record on ClinicalTrials.gov ↗

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