A multicenter, randomized, placebo-controlled, double-blind study on the efficacy, safety and tolerability of Certican® in preventing end-stage renal disease (ESRD) in patients with autosomal dominant polycystic kidney disease (ADPKD) - ADPKD

• Conditions: polycystic kidney disease; MedDRA version: 8.1Level: LLTClassification code 10011771Term: Cystic kidney disease

• Registration Number: EUCTR2006-001485-16-FR
• Lead Sponsor: ovartis Pharma GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07-23
• Last Update Posted: 4 August 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1.Males or females, aged 18 – 65 years
2.Clinical diagnosis of autosomal dominant polycystic kidney disease (ADPKD), (Appendix 6)
3.CKD stage II/III, i.e. calculated GFR (MDRD formula) (ml/min/1.73 m²) has to be 30 - 89
or
CKD I, i.e. calculated GFR (MDRD formula) (ml/min/1.73 m²) is = 90 and a kidney volume (estimated by ultrasound) > 1000 mL
4.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 (see Section 8.2)
5.Patients who are willing and able to participate in the study and from whom written informed consent has been obtained

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.CKD I (a calculated GFR = 90 mL/min/1.73m2) and a kidney volume (estimated by ultrasound) of = 1000 ml
2.Patients with CKD stage IV (a calculated GFR < 30 mL/min/1.73m2)
3.Patients with a history of subarachnoid bleeding
4.Patients with a history of serious 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
8.Patients with any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or any known hypersensitivity to Certican®, other drugs similar to Certican® (e.g., macrolides), or other components of the formulations (e.g. lactose)
9.Patients with any surgical or medical condition, which in the opinion of the investigator, preludes enrollment in the trial
10.Evidence of severe liver disease (incl. abnormal liver enzyme profile, i.e. AST, ALT, AP or total bilirubin > 3 times UNL)
11.Patients who are HIV positive or Hepatitis B surface antigen positive or who are known to have chronic active Hepatitis C. Laboratory results obtained within 6 months prior to baseline are acceptable
12.Patients with symptoms of significant somatic or mental illness. Inability to cooperate or communicate with the investigator, who are unlikely to comply with the study requirements, or who are unable to give informed consent
13.Patients with unresolved history or evidence of drug or alcohol abuse
14.Presence of severe hypercholesterolemia (= 350 mg/dL, 9.1 mmoL/L), or hypertriglyceridemia (= 500 mg/dL, 5.6 mmoL/L), if hyperlipidemia is not sufficiently controlled by fluvastatines
15.Patients with white blood cell count count = 4,000/mm³, or platelet count = 100,000/mm³
16.Patients with a history of malignancy during the last five years, except for successfully treated localized squamous or basal cell carcinoma of the skin
17.Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation (low-dose aspirin treatment is allowed)
18.Patients with abnormal physical or laboratory findings of clinical significance within two weeks prior to randomization which at the investigators discretion would interfere with the objectives of the study
19.Females of childbearing potential who are planning to become pregnant, who are pregnant or breast feading, and/or who are unwilling to use effective means of contraception during the study period and until six weeks after discontinuation of study medication.
20.Patients with a contraindication against MRI

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this trial is to demonstrate that everolimus (Certican®) has superior efficacy compared with placebo in reducing the mean total kidney volume from baseline to 24 months of treatment in patients with ADPKD.;Secondary Objective: Secondary objectives of this trial are:<br>•To assess changes from baseline at Month 24 in mean cyst and parenchyma volumes<br>•To assess changes in renal function between baseline and Month 24 as assessed by calculated GFR (MDRD formula), serum creatinine, and proteinuria<br>•To assess incidence of end-stage renal disease (ESRD), defined by the requirement for renal replacement therapy<br>•To assess changes from baseline at Month 24 in blood pressure<br>•To assess the overall survival<br>•To assess safety and tolerability of the study drug;Primary end point(s): The primary variable for assessment of total kidney volume measured by MRI is the change from baseline in total renal volume [ml/year] at Month 24.