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)
Otsuka Pharmaceutical Development & Commercialization, Inc.
Phase
Phase 3
Started
2023-01-23
Last updated
2026-08-07
Condition(s) studied
Autosomal Recessive Polycystic Kidney (ARPKD)
Investigational drug(s) / intervention(s)
Tolvaptan SuspensionTolvaptan Tablets
Tolvaptan Suspension: Syrup
Tolvaptan Tablets: Tolvaptan (OPC-41061) Tolvaptan tablets will be administered orally as split-dose regimens (15/7.5 mg, 30/15 mg, and 45/15 mg) upon awakening and 8 hours later (twice daily) based on weight if able to swallow tablets.
Study summary
To evaluate the pharmacodynamics and safety of tolvaptan in pediatric subjects with ARPKD
Eligibility
Sex
ALL
Min age
28 Days
Max age
18 Years
Healthy volunteers
No
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.
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 (upper limit of normal).
5. Has splenomegaly or portal hypertension (HTN).
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 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.
15. Taking any other experimental medications.
16. Require ventilator support.
17. Taking medications known to induce CYP3A4 (CYP = Cytochrome P).
18. Having an infection including viral that would require therapy disruptive to IMP (Investigational Medicinal Product) 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 taking a vasopressin agonist (eg, desmopressin).
23. Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy.
24. 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).
25. Received or are scheduled to receive a liver transplant.
26. History of cholangitis within the last 6 months.
27. Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia).
28. 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.
Primary outcome measure(s)
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) — From baseline to post-treatment after 24 months or EoTx Number of participants with TEAEs will be assessed from Baseline to post-treatment after 24 months or End of Treatment (EOTx). The EOTx visit applies to participants who discontinue IMP before Month 24. TEAEs are defined as Adverse Events (AEs) with an onset date on or after the start of Investigational Medicinal Product (IMP) treatment. TEAEs are also events continuous from baseline which worsened, became serious, were IMP related, or resulted in death, discontinuation, interruption, or reduction of IMP. An AE is defined as any untoward medical occurrence in a clinical trial subject administered an IMP and which does not necessarily have a causal relationship with this treatment.
Trial sites (23)
Facility
City
Region
Status
Children's National Medical Center
Washington D.C.
District of Columbia
Recruiting
Emory University Hospital
Atlanta
Georgia
Withdrawn
Northwestern University Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago - Neonatology
Chicago
Illinois
Withdrawn
Riley Hospital for Children
Indianapolis
Indiana
Withdrawn
Children's Hospital - New Orleans
New Orleans
Louisiana
Withdrawn
Johns Hopkins Pediatric Specialty Clinic
Baltimore
Maryland
Recruiting
C.S. Mott Children's Hospital
Ann Arbor
Michigan
Recruiting
Mayo Clinic - Rochester
Rochester
Minnesota
Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati
Ohio
Recruiting
Cleveland Clinic
Cleveland
Ohio
Recruiting
Children's Hospital of Pittsburgh of UPMC
Pittsburgh
Pennsylvania
Withdrawn
Primary Children's Hospital
Salt Lake City
Utah
Withdrawn
Université Catholique De Louvain And Cliniques St Luc
Brussels
Brussels Capital
Recruiting
Universitair Ziekenhuis Gent
Ghent
Oost-Vlaanderen
Recruiting
UZ Leuven
Leuven
Vlaams Brabant
Recruiting
Universitätsklinikum Köln
Cologne
North Rhine-Westphalia
Recruiting
Instytut "Pomnik - Centrum Zdrowia Dziecka"
Warsaw
Masovian Voivodeship
Withdrawn
Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
Bialystok
Poland
Withdrawn
Universitat de Barcelona - Hospital Sant Joan de Deu Barcelona (HSJDB)
Esplugues de Llobregat
Barcelona
Recruiting
Hospital Universitari Parc Tauli
Sabadell
Barcelona
Withdrawn
Hospital Universitari Vall D Hebron
Barcelona
Spain
Recruiting
Hospital Universitario Virgen del Rocío Avenida Manuel Siurot
Seville
Spain
Withdrawn
Great Ormond Street Hospital for Children NHS Trust
London
United Kingdom
Recruiting
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This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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