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)

• Status: Not yet recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of this study is to evaluate the safety of tolvaptan in pediatric subjects with autosomal recessive polycystic kidney disease (ARPKD)

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Treatments: Tolvaptan

Criteria

Inclusion Criteria:

1. Male or female subjects from Trial 156-12-204 who have completed treatment or male or female subjects between 28 days and less than 18 years of age, who have been diagnosed with a clinical diagnosis of ARPKD.

2. Ability for parent or 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.

3. Ability to commit to remain fully abstinent or use two approved methods of birth control.

(periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] or withdrawal are not acceptable methods of contraception) during the trial and for 30 days following the last dose of IMP for sexually active females of childbearing potential.

Exclusion Criteria:

1. Premature birth (≤ 32 weeks gestational age).

2. Anuria or RRT.

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 HTN.

6. Parents with renal cystic disease.

7. Need for chronic diuretic use.

8. Cannot be monitored for fluid balance.

9. Critical electrolyte imbalances, as determined by the investigator.

10. Has or at risk of having significant hypovolemia 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.

15. Cannot be taking any other experimental medications.

16. Require ventilator support.

17. Taking medications known to induce CYP3A4.

18. Having an 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).

21. Subjects who have bladder dysfunction and/or difficulty voiding.

22. Subjects 12 years of age and older having contraindications to, or interference with MRI assessments (eg, ferro-magnetic prostheses, aneurysm clips, severe claustrophobia).

23. Subjects taking a vasopressin agonist (eg, desmopressin).

24. Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy.

25. 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 RNA therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin).

CYP = Cytochrome P; HTN = hypertension; RNA = ribonucleic acid; ULN = upper limit of normal