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)
- Conditions
- Autosomal Recessive Polycystic Kidney DiseaseTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 20
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.
Premature birth (= 32 weeks gestational age)., Receiving chronic diuretic that could not be adjusted after tolvaptan initiation., Cannot be monitored for fluid balance., Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator., Taking any other experimental medications., Require ventilator support., Taking medications known to induce CYP3A4., Having an active infection including viral that would require therapy disruptive to IMP dosing., Platelet count <50,000 µL., Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia)., 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)., 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)., History of cholangitis., Received or are scheduled to receive a liver transplant., 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)., Clinically significant anemia, as determined by investigator., 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)., Abnormal liver function tests including ALT and AST, > 1.2 × ULN., Parents with renal cystic disease.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of tolvaptan on the need for RRT in pediatric subjects with ARPKD.;Secondary Objective: Evaluate changes in eGFR and palatability and acceptability of formulation., To evaluate the pharmacodynamics, safety, tolerability, and efficacy of tolvaptan in pediatric subjects with ARPKD.;Primary end point(s): Primary Efficacy: Percentage of subjects having RRT by 1 year of age
- Secondary Outcome Measures
Name Time Method