Pulsed oral sirolimus in autosomal dominant polycystic kidney disease

Phase 1

Conditions: 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: 20.0Level: LLTClassification code 10036046Term: Polycystic kidney, autosomal dominantSystem Organ Class: 100000004850
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2012-000550-60-AT

Lead Sponsor: Medizinische Universität Wien, Klinische Abteilung für Nephrologie und Dialyse, Universitätsklinik für Innere Medizin 3

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 68

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

• 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