A Study to See if Tolvaptan is Safe in Infants and Children Who at Enrollment Are 28 Days to Less Than 18 Years Old With Autosomal Recessive Polycystic Kidney Disease (ARPKD)

Prior treatment

• Receiving chronic diuretic that could not be adjusted after tolvaptan initiation.
• Taking any other experimental medications.
• Taking medications known to induce CYP3A4 (CYP = Cytochrome P).
• Females who are breast-feeding or who have a positive pregnancy test result prior to receiving IMP.
• Subjects taking medications or having concomitant illnesses likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting PKD cysts such as tolvaptan, vasopressin antagonists, anti-sense ribonucleic acid (RNA) therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin).
• Received or are scheduled to receive a liver transplant.
• Subjects who do not agree to remain abstinent or assent to use a combination of 2 of the following highly effective birth control methods for at least 28 days before the first dose of IMP, during the trial (including during IMP dose interruptions), and for at least 30 days after the last dose of IMP:
  • Barrier method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide
  • Intrauterine device
  • Hormone-based contraceptives which are associated with inhibition of ovulation.

Other illness

• Anuria or RRT defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration or history of kidney transplantation.
• Evidence of syndromic conditions associated with renal cysts (other than ARPKD).
• Has splenomegaly or portal hypertension (HTN).
• Parents with renal cystic disease.
• Having an infection including viral that would require therapy disruptive to IMP (Investigational Medicinal Product) dosing.
• Subjects with a history of substance abuse (within the last 6 months).
• Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy.
• History of cholangitis within the last 6 months.
• Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia).

Lab values

• Abnormal liver function tests including ALT and AST, \> 1.2 × ULN (upper limit of normal).
• Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator.
• Platelets \< 50000 µL.
• Severe systolic dysfunction defined as ejection fraction \< 14%.
• Serum sodium levels \< 130 mmol/L or \>145 mmol/L.

Age

• Premature birth (≤ 32 weeks gestational age) for infants 28 days to \< 12 weeks of age.

Other

• Cannot be monitored for fluid balance.
• Has or at risk of having significant hypovolemia as determined by investigator.
• Clinically significant anemia, as determined by investigator.
• Require ventilator support.
• Subjects who have bladder dysfunction and/or difficulty voiding.
• Subjects taking a vasopressin agonist (eg, desmopressin).

• Male or female subjects between 28 days and less than 18 years of age, with clinical features that are consistent with a diagnosis of ARPKD.
• Ability for parent/legal guardian to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial. Ability to provide written informed assent from all subjects old enough per local laws to provide assent.