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RecruitingNCT04782258Updated Aug 7, 2026

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)

A Phase 3 interventional study of Tolvaptan Suspension and Tolvaptan Tablets in Autosomal Recessive Polycystic Kidney (ARPKD), sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Recruiting at 23 sites in 6 countries. Open to participants aged 28 Days to 18 Years. Per ClinicalTrials.gov, last updated 2026-08-07.

Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
20
Allocation
Non-randomized
Ages
28 Days to 18 Years
Sex
All
01

Study summary

To evaluate the pharmacodynamics and safety of tolvaptan in pediatric subjects with ARPKD

Read the detailed description

This study is a multinational, multicenter, open-label, non-randomized trial. The study consist of three periods: Screening Period, Treatment period and Follow-up period.

Tolvaptan has been demonstrated to delay the decline of kidney function in adults with rapidly progressing ADPKD (CKD stages 1 to 4), a closely related indication to ARPKD, as measured by estimated glomerular filtration rate (eGFR) and Total Kidney Volume (TKV).

Participants in this study will be assigned to tolvaptan and followed for 24 months over the course of the study.

The overall trial duration is expected to be approximately 5 years.

02

Conditions studied

  • Autosomal Recessive Polycystic Kidney (ARPKD)

Keywords

  • ARPKD
  • TOLVAPTAN
  • Polycystic Kidney Disease
  • Autosomal Recessive Polycystic Kidney Disease
  • Adolescent
  • Renal Cysts
  • Oligohydramnios
  • Anhydramnios
03

Who can participate

Ages eligible
28 Days to 18 Years
Sexes eligible
All
Accepts 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

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.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
20 participants (estimated)

Study arms

  • Experimental
    Tolvaptan Suspension

    Tolvaptan suspension will be administered orally or via feeding/nasogastric tube at doses of 0.15 mg/kg once daily in the AM, 0.30 mg/kg once daily in the AM, 0.5 mg/kg once daily in the AM, 0.75 mg/kg split dose (0.5 mg/kg AM and 0.25 mg/kg 8 hours later), and 1 mg/kg split dose (0.67 mg/kg AM and 0.33 mg/kg 8 hours later) based on age. Treatment duration is 24 months.

    Drug: Tolvaptan Suspension

  • Experimental
    Tolvaptan Tablets

    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. Treatment duration is 24 months.

    Drug: Tolvaptan Tablets

Interventions

  • DrugTolvaptan Suspension

    Syrup

  • DrugTolvaptan 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.

05

What researchers measure

Primary outcomes

  1. Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)

    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.

    Time frame: From baseline to post-treatment after 24 months or EoTx

Secondary outcomes

  1. Annual rate of change of eGFR (by Schwartz formula) from baseline to post-treatment after 24 months

    Annual rate of change of eGFR from Baseline to post-treatment after Month 24 or EOTx is calculated using eGFR Schwartz formula = 0.413 × height \[or length, centimeter (cm)\] /serum creatinine milligram per deciliter (mg/dL). The EOTx visit applies to participants who discontinue IMP before Month 24.

    Time frame: From Baseline to post-treatment after Month 24 or EOTx

  2. Change from baseline of eGFR (by Schwartz formula) while on treatment at Months 1, 6, 12, 18 and 24 or EOTx

    Change from baseline of eGFR is calculated using eGFR Schwartz formula = 0.413 × height \[or length, cm\] /serum creatinine mg/dL) while on treatment at Months 1, 6, 12, 18, and 24 or EoTx. The EOTx visit applies to participants who discontinue IMP before Month 24.

    Time frame: At Months 1, 6, 12, 18, and 24 or EOTx

  3. The amount of time between enrollment and 24 months that a subject requires renal replacement therapy (RRT).

    To evaluate the effect of tolvaptan on the need for RRT in pediatric participants with ARPKD.

    Time frame: From enrollment to 24 months

  4. The percentage of subjects that will receive renal replacement therapy (RRT) by 24 months

    Percentage of subjects who receive RRT from baseline through Month 24. RRT is defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration or kidney transplantation.

    Time frame: From Baseline to Month 24

06

Study locations

13 of 23 sites recruiting
  • Children's National Medical Center
    Washington D.C., District of Columbia 20010, United States
    Recruiting
  • Emory University Hospital
    Atlanta, Georgia 30322, United States
    Withdrawn
  • Northwestern University Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago - Neonatology
    Chicago, Illinois 60611, United States
    Withdrawn
  • Riley Hospital for Children
    Indianapolis, Indiana 46202-5119, United States
    Withdrawn
  • Children's Hospital - New Orleans
    New Orleans, Louisiana 70118, United States
    Withdrawn
  • Johns Hopkins Pediatric Specialty Clinic
    Baltimore, Maryland 21287, United States
    Recruiting
  • C.S. Mott Children's Hospital
    Ann Arbor, Michigan 48109-5000, United States
    Recruiting
  • Mayo Clinic - Rochester
    Rochester, Minnesota 55905, United States
    Recruiting
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229-3039, United States
    Recruiting
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
    Recruiting
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15213, United States
    Withdrawn
  • Primary Children's Hospital
    Salt Lake City, Utah 84113, United States
    Withdrawn
  • Université Catholique De Louvain And Cliniques St Luc
    Brussels, Brussels Capital 1200, Belgium
    Recruiting
  • Universitair Ziekenhuis Gent
    Ghent, Oost-Vlaanderen 9000, Belgium
    Recruiting
  • UZ Leuven
    Leuven, Vlaams Brabant 3000, Belgium
    Recruiting
  • Universitätsklinikum Köln
    Cologne, North Rhine-Westphalia 50937, Germany
    Recruiting
  • Instytut "Pomnik - Centrum Zdrowia Dziecka"
    Warsaw, Masovian Voivodeship 04-730, Poland
    Withdrawn
  • Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
    Bialystok, 15-274, Poland
    Withdrawn
  • Universitat de Barcelona - Hospital Sant Joan de Deu Barcelona (HSJDB)
    Esplugues de Llobregat, Barcelona 8950, Spain
    Recruiting
  • Hospital Universitari Parc Tauli
    Sabadell, Barcelona 08208, Spain
    Withdrawn
  • Hospital Universitari Vall D Hebron
    Barcelona, 8035, Spain
    Recruiting
  • Hospital Universitario Virgen del Rocío Avenida Manuel Siurot
    Seville, 41013, Spain
    Withdrawn
  • Great Ormond Street Hospital for Children NHS Trust
    London, WC1N 3JH, United Kingdom
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT04782258
Lead sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Responsible party
Sponsor
First posted
Mar 4, 2021
Start date
Jan 23, 2023
Primary completion
Jul 31, 2028 (estimated)
Completion
Aug 14, 2028 (estimated)
Last update
Aug 7, 2026

Study contacts

Otsuka Call Center
Contact
Otsuka-ProfessionalServices@otsuka-us.com
844-687-8522

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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