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

NCT00414440 | Completed Phase 4 Results

• 2 other identifiers: CRAD001ADE122006-001485-16
• Study Type: interventional
• Target: 431
• Locations: 3 countries
• Sites: 24

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.

Conditions

Autosomal Dominant Polycystic Kidney Disease

Keywords

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

Outcome Measures

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.

  Baseline, Month 24

Secondary Outcomes (4)

• Course of Calculated GFR (mL/Min/1.73 m^2) From Month 24 to Month 60

  Months 24, 36, 48 and 60

• Calculated GFR, Change From Baseline at Month 60 by Baseline cGFR

  Months 24, 36, 48 and 60

• Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline, 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

Study Arms (2)

Everolimus

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

placebo comparator

Placebo

Everolimus DRUG

experimental

Also known as: certican

Everolimus

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (24)

Novartis Investigative Site

Innsbruck, INNSBRUCK, Austria

Location

Novartis Investigative Site

Linz, A-4010, Austria

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Brest, 29200, France

Location

Novartis Investigative Site

Grenoble, 38043, France

Location

Novartis Investigative Site

Nantes, 44035, France

Location

Novartis Investigative Site

Paris, 75015, France

Location

Novartis Investigative Site

Toulouse, 31054, France

Location

Novartis Investigative Site

Berlin, 10117, Germany

Location

Novartis Investigative Site

Berlin, 13353, Germany

Location

Novartis Investigative Site

Cologne, 51109, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Frankfurt am Main, 60596, Germany

Location

Novartis Investigative Site

Freiburg im Breisgau, 79106, Germany

Location

Novartis Investigative Site

Hamburg, 20246, Germany

Location

Novartis Investigative Site

Heidelberg, 69120, Germany

Location

Novartis Investigative Site

Homburg, 66421, Germany

Location

Novartis Investigative Site

Kiel, 24105, Germany

Location

Novartis Investigative Site

Leipzig, 04103, Germany

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Regensburg, 93053, Germany

Location

Novartis Investigative Site

Würzburg, 97080, Germany

Location

Related Publications (2)

• St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.

  PMID: 39356039 DERIVED

• 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.

  PMID: 20581392 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Polycystic Kidney, Autosomal Dominant; Kidney Failure, Chronic

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Polycystic Kidney Diseases; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Ciliopathies; Genetic Diseases, Inborn; Renal Insufficiency, Chronic; Renal Insufficiency; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Study Director
• Organization: Novartis

+1 (862) 778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2006
• First Posted: December 21, 2006
• Study Start: December 1, 2006
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: January 14, 2015
• Results First Posted: January 14, 2015

Record last verified: 2015-01

Locations

DE (16); FR (5); AU (3)