Tolvaptan-Octreotide LAR Combination in ADPKD

Inclusion criteria

• Adult (>18-yr-old) men and women, with a clinical and ultrasonographic diagnosis of ADPKD;
• Serum creatinine < 1.0 mg/dl (for man) and < 1.2 mg/dl (for woman) and changes in serum creatinine (and creatinine clearance when available) <30% over the last six months;
• Creatinine clearance > 80 ml/min/1.73m2 measured one to two weeks apart during the pre-screening period;
• GFR ≥ 80 ml/min/1.73m2 (by iohexol plasma clearance technique) at screening and baseline evaluations;
• TKV ranging between 1000 and 2000 ml at screening (by ultrasound imaging) and at baseline (by MRI) evaluations;
• Female participants must be of non-childbearing potential or must agree to abstinence or use a highly effective form of contraception;
• Written informed consent.

Exclusion criteria

• Patients with concomitant systemic, renal parenchymal or urinary tract disease;
• Diabetes;
• Overt proteinuria (urinary protein excretion rate >1 g/24 hours);
• Abnormal urinalysis suggestive of concomitant, clinically significant glomerular disease, urinary tract lithiasis, infection or obstruction, biliary tract lithiasis or obstruction;
• Hemorrhagic or complicated cysts which might acutely affect kidney function and volumes;
• QT-related ECG abnormalities;
• Cancer and major systemic diseases that could prevent completion of the planned follow-up or interfere with data collection or interpretation;
• Hypersensitivity to the IMP active substance or to any of the excipients or to benzazepine or benzazepine derivatives;
• Concomitant treatment with drugs that may affect glomerular hemodynamics during the three months before the beginning of the study (including ACE inhibitors, angiotensin receptor blockers, aldosterone antagonists and non-steroideal anti-inflammatory medications);
• Elevated liver enzymes and/or signs or symptoms of liver injury prior to initiation of treatment that meet the requirements for permanent discontinuation of tolvaptan
• Patients with anuria, volume depletion and hypernatraemia
• Patients who cannot perceive or respond to thirst
• Ferro-magnetic prosthesis, aneurysm clips, severe claustrophobia or any other contraindication to MRI evaluation;
• Psychiatric disorders and any condition that could prevent full comprehension of the purposes and risks of the study;
• Pregnant or lactating;
• Participation in another interventional clinical trial within the 4 weeks prior to screening.