Metformin versus Tolvaptan in adults with Autosomal Dominant Polycystic Kidney Disease (ADPKD): a phase 3a, independent, multi-centre, 2 parallel arms randomized controlled trial

Prior treatment

• Women who are breast-feeding and/or who have a positive pregnancy test result prior to receiving investigational medical product (IMP).
• Treatment with acarbose, guar gum, cimetidin, phenprocoumon, oral anticoagulants, thrombolytic drugs, diuretics, ranolazin, cephalexin.
• Previously diagnosed diabetes already in treatment with other hypoglycemic drugs.
• Use of any other investigational drug or treatment up to 4 weeks before enrollment and during the treatment phase.

Other illness

• Known hypersensitivity to metformin and its derivatives.
• Psychiatric disorders and any condition that might prevent full comprehension of the purposes and risks of the study.
• Malignancies within three years before enrolment in the study.
• HIV, HBV, HCV infection.
• Evidence of active systemic or localized major infection at the time of screening.
• Acute or chronic disease causing tissue hypoxia (e.g.: myocardial failure, severe arythmias, myocardial infarction, respiratory failure, liver failure, alcohol acute intoxication, alcoholism, dehydration).

Lab values

• Hepatic impairment or liver function abnormalities other than that expected for ADPKD with typical cystic liver disease during the screening period as defined by: AST or ALT >8x UNL; AST or ALT >5x UNL >2 WEEKS; AST or ALT >3x UNL and BT >2x UNL OR INR >1,5; AST or ALT >3x UNL and SIGNS AND SYMPTOMS OF LIVER DAMAGE (fatigue, anorexy, nausea, vomiting, right hypocondrium pain, fever, jaundice, skin rash, itching)

Other

• Women of childbearing potential (WOCBP) who do not agree to practice 2 different methods of birth control or remain abstinent during the trial and for 30 days after the last dose of IMP. If employing birth control, 2 of the following precautions must be used: vasectomy of partner, tubal ligation, vaginal diaphragm, intrauterine device, condom, or sponge with spermicide. Non childbearing potential in women is defined as female subjects who are surgically sterile (ie, have undergone bilateral oophorectomy or hysterectomy) or female subjects who have been postmenopausal for at least 12 consecutive months.
• Urinary tract obstruction.
• Ongoing breast feeding.

• Men and women aged between 18 and 55 years
• mean of eGFR (CKD-EPI) in SV1 and SV2 ≥ 45 ml/min/1,73 m2
• Genetic Diagnosis of Type I ADPKD truncating mutation
• Signed and dated informed consent