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)

• Register: EUCTR
• Last refreshed on: 26 August 2024
• Main ID: EUCTR2020-005992-10-DE
• Date of registration: 26/05/2021
• Prospective Registration: Yes
• Primary sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
• Public title: 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)
• Scientific 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)
• Target sample size: 10
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-005992-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czechia, France, Germany, Italy, Poland, Spain, United Kingdom, United States

Contacts

• Name: Mathew Taylor
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

• Name: Mathew Taylor
• Affiliation: Otsuka Pharmaceutical Development & Commercialization, Inc.

Key inclusion & exclusion criteria

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Autosomal Recessive Polycystic Kidney Disease (ARPKD)
MedDRA version: 20.0 Level: LLT Classification code 10036047 Term: Polycystic kidney, autosomal recessive System Organ Class: 100000004850

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Trade Name: SAMSCA 7.5 mg oral tablet
Product Name: Tolvaptan 7.5 mg Tablet
Product Code: OPC-41061
Pharmaceutical Form: Tablet
INN or Proposed INN: Tolvaptan
CAS Number: 150683-30-0
Current Sponsor code: OPC-41061
Other descriptive name: TOLVAPTAN (OPC-41061)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7.5-

Trade Name: Jinarc® 15mg Tablet
Product Name: Tolvaptan 15 mg Tablet
Product Code: OPC-41061
Pharmaceutical Form: Tablet
INN or Proposed INN: Tolvaptan
CAS Number: 150683-30-0
Current Sponsor code: OPC-41061
Other descriptive name: TOLVAPTAN (OPC-41061)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-

Trade Name: Jinarc 30 mg Tablet
Product Name: Tolvaptan 30 mg Tablet
Product Code: OPC-41061
Pharmaceutical Form: Tablet
INN or Proposed INN: Tolvaptan
CAS Number: 150683-30-0
Current Sponsor code: OPC-41061
Other descriptive name: TOLVAPTAN (OPC-41061)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Product Name: Tolvaptan 50mg Granules
Product Code: OPC-41061
Pharmaceutical Form: Granules for oral suspension
INN or Proposed INN: Tolvaptan
CAS Number: 150683-30-0
Current Sponsor code: OPC-41061
Other descriptive name: TOLVAPTAN (OPC-41061)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Secondary Objective: To evaluate the effect of tolvaptan on the need for RRT in pediatric subjects with ARPKD

Primary end point(s): Safety assessments which will be summarized by descriptive statistics, and the endpoints will be
- Adverse events
- Vital signs
- Clinical laboratory assessments
- Serum transaminase elevations for frequency (2 ×, 3 ×, 5 × and 10 × ULN), time to onset, time to peak levels, time of offset (< 3 ×, 2 ×, or 1 × ULN), response to de-challenge and re-challenge and frequency of progression to Hy’s laboratory criteria (ALT or AST > 3 × ULN and BT, > 2 × ULN without alkaline phosphatase greater than or equal to 2 × ULN)
- Change from baseline in sNa+

Main Objective: To evaluate the safety of tolvaptan in pediatric subjects with ARPKD

Timepoint(s) of evaluation of this end point: Months 1, 6, 12, and 18

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Months 1, 6, 12, and 18

Secondary end point(s): Annual rate of change of eGFR (eGFR Schwartz formula = 0.413 × height [or length, cm] /serum creatinine mg/dL) from baseline to post-treatment after 18 months of treatment
-Change from baseline of eGFR (eGFR
Schwartz formula = 0.413 × height [or length, cm] /serum creatinine mg/dL) while on treatment at Months 1, 6, 12, and 18
-Time to RRT
-Percentage of subjects who receive RRT

Secondary ID(s)

156-201-00307

NCT04782258

Source(s) of Monetary Support

Otsuka Pharmaceutical Development & Commercialization, Inc.