A trial 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)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 10

Inclusion Criteria

1. 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.
2. 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Premature birth (= 32 weeks gestational age) for infants 28 days to <12 weeks of age.
2. Anuria or RRT defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration or history of kidney transplantation
3. Evidence of syndromic conditions associated with renal cysts (other than ARPKD)
4. Abnormal liver function tests including ALT and AST, > 1.2 × ULN
5. Has splenomegaly or portal hypertension
6. Parents with renal cystic disease
7. Receiving chronic diuretic that could not be adjusted after tolvaptan initiation.
8. Cannot be monitored for fluid balance
9. Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator
10. Has or at risk of having significant hypovolemia (e.g. subjects that lack free access to water
[inability to respond to thirst, depending on age], without adequate fluid monitoring and
management) as determined by investigator
11. Clinically significant anemia, as determined by investigator
12. Platelets < 50000 µL
13. Severe systolic dysfunction defined as ejection fraction < 14%
14. Serum sodium levels < 130 mmol/L or >145 mmol/L (or the ULN of the local laboratory, whichever is lower)
15. Taking any other experimental medications
16. Require ventilator support
17. Taking medications known to induce CYP3A4
18. Having an active infection including viral that would require therapy disruptive to IMP dosing
19. Females who are breast-feeding or who have a positive pregnancy test result prior to receiving IMP.
20. Subjects with a history of substance abuse within the last 6 months (depending on age).
21. Subjects who have bladder dysfunction and/or difficulty voiding.
22. Subjects taking a vasopressin agonist (eg, desmopressin).
23. Subjects with a history of persistent non-compliance with antihypertensive or other important medical therapy
24. 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).
25. Subjects who do not agree to remain abstinent or assent to use a combination of two 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 with or without a spermicidal agent, diaphragm or cervical cap with spermicide, Intrauterine device, Hormone-based contraceptives which are associated with inhibition of ovulation.
26. Received or are scheduled to receive a liver transplant.
27. History of cholangitis within the last 6 months
28. Has findings consistent with clinically significant portal hypertension (eg, varices, variceal
bleeding, hypersplenism indicated by thrombocytopenia

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials

A Phase 3b Multicenter Open-label Trial of the Safety, Tolerability, and Efficacy of Tolvaptan in Infants and Children 28 days to less than 18 years of Age with Autosomal Recessive Polycystic Kidney Disease (ARPKD)

RecruitingPhase 1

Otsuka Pharmaceutical Development & Commercialization Inc.

Updated 8/21/2024