A Phase 3b Multicenter Open-label Trial of the Safety, Tolerability, and Efficacy of Tolvaptan in Infants and Children 28 days to less than 12 weeks of Age 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.
• Subjects having concomitant illnesses or taking medications 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 RNA therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin).
• Received or are scheduled to receive a liver transplant.

Other illness

• Having an active infection including viral that would require therapy disruptive to IMP dosing.
• Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia).
• History of cholangitis.
• 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).
• Parents with renal cystic disease.

Lab values

• Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator.
• Platelet count <50,000 µL.
• Severe systolic dysfunction defined as ejection fraction < 14%.
• Serum sodium levels < 130 mmol/L or >145 mmol/L (or the ULN of the local laboratory, whichever is lower).
• Abnormal liver function tests including ALT and AST, > 1.2 × ULN.

Age

• Premature birth (≤ 32 weeks gestational age).

Other

• Cannot be monitored for fluid balance.
• Require ventilator support.
• Subjects who have bladder dysfunction and/or difficulty voiding.
• Has or at risk of having significant hypovolemia (eg, subjects that lack free access to water, without adequate fluid monitoring and management) as determined by investigator.
• Subjects taking a vasopressin agonist (eg, desmopressin).
• Clinically significant anemia, as determined by investigator.

• Male or female subjects between 28 days and < 12 weeks of age, inclusive.
• Must have clinical and imaging features that are consistent with a diagnosis of ARPKD with all the following characteristics: Nephromegaly (> 2 standard deviations from age-appropriate standard via ultrasound) Multiple renal cysts History of oligohydramnios or anhydramnios.
• 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.