Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the development and uncontrolled proliferation of innumerable epithelial-lined cysts that stem from renal tubular cells, which compress and/or destroy vital renal tissue with a gradual decline in renal function, and terminal kidney failure with the need for renal reaplacement therapy. As yet, other than supportive care there is no viable therapy. MedDRA version: 20.0 Level: LLT Classification code 100360
Conditions
Interventions
Trade Name: Rapamune 1mg tablets
Product Name: Rapamune 1mg tablets
Pharmaceutical Form: Coated tablet
INN or Proposed INN: SIROLIMUS
CAS Number: 53123-88-9
Concentration unit: mg milligram(s)
Concent
Sponsors
Medizinische Universität Wien, Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin 3
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • ADPKD, as confirmed by history, ultrasound, computed- or magnetic resonance tomography • Eighteen years of age, or older • Baseline estimated glomerular filtration rate (eGFR; 4 variable MDRD equation) below 60 mL/min per 1.73m2 • Negative serum pregnancy test prior to administration of sirolimus and agreement to use contraception throughout the study and three months after • Written informed consent 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 68 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: • Need for renal replacement therapy • Pregnancy/lactation • Plans to become pregnant in the near future • Refusal to use sufficient contraception • Proteinuria as defined as proteine:creatinine ratio >1000 or >1g/d, respectively • History of life threatening complications of ADPKD • Evidence of active systemic- or localized major infection • Evidence of infiltrate or consolidation on chest X-ray • Use of any investigational drug or -treatment up to 4 weeks prior to enrolment and during the study • Known allergy/hypersensitivity to sirolimus and its derivatives • Medication that will interfere with the CYP3A4/CYP3A5 system • Total white blood cell count below or equal to 3000/mm3 • Platelet count below or equal to 100.000/mm3 • Fasting triglycerides above or equal to 400 mg/dL • Fasting total cholesterol above or equal to 300 mg/dL • Concomitant glomerular diseases • Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study • History of malignancy, with the exception of adequately treated basal cell- and squamous cell carcinoma of the skin • HIV positivity
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Tubular cells, the target of mTOR-I in ADPKD, develop a resistance towards sirolimus in vitro as well as in vivo with continuous exposure to the drug. Pulsed administration of the mTOR-inhibitor sirolimus in a fixed weekly oral dose of 3 mg compared to placebo significantly reduces cyst growth and preserves excretory renal function in patients with autosomal-dominant polycystic kidney disease and an estimated glomerular filtration rate below 60 mL/min per 1.73m2. Null hypothesis: Pulsed administration of the mTOR-inhibitor sirolimus in a fixed weekly oral dose of 3 mg compared to placebo does not reduce cyst growth and preserve excretory renal function in patients with autosomal-dominant polycystic kidney disease and an estimated glomerular filtration rate below 60 mL/min per 1.73m2.;Secondary Objective: Safety, change in proteinuria, as indicated by albumin/creatinine- and protein/creatinine ratio, respectively.;Primary end point(s): Fifty percent reduction in doubling of serum creatinine, or initiation of dialysis over a period of two years. Less or equal than 1.5 fold increase in serum creatinine without initiation of dialysis over two years is considered a beneficial outcome, increases in serum creatinine greater than 1.5 over two years or initiation of dialysis are considered a nonbeneficial outcome. ;Timepoint(s) of evaluation of this end point: After 24 months of therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety, change in proteinuria, as indicated by albumin/creatinine- and protein/creatinine ratio, respectively.;Timepoint(s) of evaluation of this end point: After 24 months of therapy. | — |
Countries
Austria
Contacts
Public ContactClinical Trials Information
Medizinische Universität Wien
Outcome results
None listed