Autosomal Recessive Polycystic Kidney (ARPKD)Phase 3NCT04782258
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 study testing Tolvaptan Suspension and Tolvaptan Tablets in people with Autosomal Recessive Polycystic Kidney (ARPKD), run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 23 sites in 6 countries.
Trial summary
To evaluate the pharmacodynamics and safety of tolvaptan in pediatric subjects with ARPKD Read more about this study
- Who is it for?
- Ages 28 days to 18 years
- Conditions the study is for
- Autosomal Recessive Polycystic Kidney (ARPKD)
- What is being tested?
- Tolvaptan Suspension and Tolvaptan Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 23 sitesin 6 countries
- Study dates
- 23 Jan 2023to 28 Dec 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 28 days to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- 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.
Who cannot join
- Premature birth (≤ 32 weeks gestational age) for infants 28 days to < 12 weeks of age.
- 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 (upper limit of normal).
- Has splenomegaly or portal hypertension (HTN).
- Parents with renal cystic disease.
Show all 31Show fewer
- 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.
- Has or at risk of having significant hypovolemia as determined by investigator.
- Clinically significant anemia, as determined by investigator.
- Platelets < 50000 µL.
- Severe systolic dysfunction defined as ejection fraction < 14%.
- Serum sodium levels < 130 mmol/L or >145 mmol/L.
- Taking any other experimental medications.
- Require ventilator support.
- Taking medications known to induce CYP3A4 (CYP = Cytochrome P).
- Having an infection including viral that would require therapy disruptive to IMP (Investigational Medicinal Product) dosing.
- Females who are breast-feeding or who have a positive pregnancy test result prior to receiving IMP.
- Subjects with a history of substance abuse (within the last 6 months).
- Subjects who have bladder dysfunction and/or difficulty voiding.
- Subjects taking a vasopressin agonist (eg, desmopressin).
- Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy.
- 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).
- Received or are scheduled to receive a liver transplant.
- History of cholangitis within the last 6 months.
- Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia).
- 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.
Trial locations and contacts
23 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
23 sites in 6 countries
United States12 sites, 6 recruiting
- Recruiting
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109-5000
- Withdrawn
Emory University Hospital
Atlanta, Georgia, 30322
- Recruiting
Johns Hopkins Pediatric Specialty Clinic
Baltimore, Maryland, 21287
- Withdrawn
Northwestern University Feinberg School of Medicine - Ann & Robert H. Lurie Children's Hospital of Chicago - Neonatology
Chicago, Illinois, 60611
- Recruiting
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Withdrawn
Riley Hospital for Children
Indianapolis, Indiana, 46202-5119
- Withdrawn
Children's Hospital - New Orleans
New Orleans, Louisiana, 70118
- Withdrawn
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15213
- Recruiting
Mayo Clinic - Rochester
Rochester, Minnesota, 55905
- Withdrawn
Primary Children's Hospital
Salt Lake City, Utah, 84113
- Recruiting
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Spain4 sites, 2 recruiting
- Recruiting
Hospital Universitari Vall D Hebron
Barcelona, 8035
- Recruiting
Universitat de Barcelona - Hospital Sant Joan de Deu Barcelona (HSJDB)
Esplugues de Llobregat, Barcelona, 8950
- Withdrawn
Hospital Universitari Parc Tauli
Sabadell, Barcelona, 08208
- Withdrawn
Hospital Universitario Virgen del Rocío Avenida Manuel Siurot
Seville, 41013
Belgium3 sites, 3 recruiting
- Recruiting
Université Catholique De Louvain And Cliniques St Luc
Brussels, Brussels Capital, 1200
- Recruiting
Universitair Ziekenhuis Gent
Ghent, Oost-Vlaanderen, 9000
- Recruiting
UZ Leuven
Leuven, Vlaams Brabant, 3000
Poland2 sites
- Withdrawn
Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa
Bialystok, 15-274
- Withdrawn
Instytut "Pomnik - Centrum Zdrowia Dziecka"
Warsaw, Masovian Voivodeship, 04-730
Germany1 site, 1 recruiting
- Recruiting
Universitätsklinikum Köln
Cologne, North Rhine-Westphalia, 50937
United Kingdom1 site, 1 recruiting
- Recruiting
Great Ormond Street Hospital for Children NHS Trust
London, WC1N 3JH
About this study
Official title: 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)
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.
- Being tested
- Tolvaptan Suspension, Tolvaptan Tablets
- Keywords
- ARPKD, TOLVAPTAN, Polycystic Kidney Disease, Autosomal Recessive Polycystic Kidney Disease, Adolescent, Renal Cysts, Oligohydramnios, Anhydramnios
- Medical subject headings
- Polycystic Kidney, Autosomal Recessive, Polycystic Kidney Diseases, Oligohydramnios
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tolvaptan SuspensionDrug
Syrup
Tolvaptan TabletsDrug
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 group | Role | What they receive |
|---|---|---|
| Tolvaptan Suspension | Experimental | 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. Receives: Drug: Tolvaptan Suspension |
| Tolvaptan Tablets | Experimental | 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. Receives: Drug: Tolvaptan Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From baseline to post-treatment after 24 months or EoTx
Secondary outcomes (4)
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.
Measured: From Baseline to post-treatment after Month 24 or EOTx
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.
Measured: At Months 1, 6, 12, 18, and 24 or EOTx
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.
Measured: From enrollment to 24 months
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.
Measured: From Baseline to Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2021
- Study start23 Jan 2023
- Primary completion28 Dec 2028 (estimated)
- Study completion28 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autosomal Recessive Polycystic Kidney (ARPKD)Studies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04782258
- Sponsor's protocol ID
- 156-201-00307
- Other IDs
- 2020-005992-10
- Status last verified
- Oct 2026
- First submitted
- 19 Feb 2021
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No