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    Summary
    EudraCT Number:2020-005992-10
    Sponsor's Protocol Code Number:156-201-00307
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2021-05-26
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedGermany - BfArM
    A.2EudraCT number2020-005992-10
    A.3Full title of the trial
    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)
    Multizentrische, offene Phase-3b-Studie zur Sicherheit, Verträglichkeit und Wirksamkeit von Tolvaptan bei Säuglingen und Kindern im Alter von 28 Tagen bis unter 18 Jahren mit autosomal-rezessiver polyzystischer Nierenerkrankung (ARPKD)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    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)
    Eine Studie zur Untersuchung der Sicherheit von Tolvaptan bei Säuglingen und Kindern, die bei Studienbeginn 28 Tage bis unter 18 Jahre alt sind und an einer autosomal rezessiven polyzystischen Nierenerkrankung (ARPKD) leiden Autosomal-rezessive polyzystische Nierenerkrankung (ARPKD)

    A.4.1Sponsor's protocol code number156-201-00307
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT04782258
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/002/2020
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorOtsuka Pharmaceutical Development & Commercialization, Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportOtsuka Pharmaceutical Development & Commercialization, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationOtsuka Pharmaceutical Development & Commercialization, Inc.
    B.5.2Functional name of contact pointMathew Taylor
    B.5.3 Address:
    B.5.3.1Street Address2440 Research Boulevard
    B.5.3.2Town/ cityRockville
    B.5.3.3Post codeMD 20850
    B.5.3.4CountryUnited States
    B.5.4Telephone number+12407804266
    B.5.5Fax number+13017218592
    B.5.6E-mailmathew.taylor-cw@otsuka-us.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name SAMSCA 7.5 mg oral tablet
    D.2.1.1.2Name of the Marketing Authorisation holderOtsuka Pharmaceutical Netherlands B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTolvaptan 7.5 mg Tablet
    D.3.2Product code OPC-41061
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTolvaptan
    D.3.9.1CAS number 150683-30-0
    D.3.9.2Current sponsor codeOPC-41061
    D.3.9.3Other descriptive nameTOLVAPTAN (OPC-41061)
    D.3.9.4EV Substance CodeSUB22755
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number7.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Jinarc® 15mg Tablet
    D.2.1.1.2Name of the Marketing Authorisation holderOtsuka Pharmaceutical Netherlands B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTolvaptan 15 mg Tablet
    D.3.2Product code OPC-41061
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTolvaptan
    D.3.9.1CAS number 150683-30-0
    D.3.9.2Current sponsor codeOPC-41061
    D.3.9.3Other descriptive nameTOLVAPTAN (OPC-41061)
    D.3.9.4EV Substance CodeSUB22755
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Jinarc 30 mg Tablet
    D.2.1.1.2Name of the Marketing Authorisation holderOtsuka Pharmaceutical Netherlands B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTolvaptan 30 mg Tablet
    D.3.2Product code OPC-41061
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTolvaptan
    D.3.9.1CAS number 150683-30-0
    D.3.9.2Current sponsor codeOPC-41061
    D.3.9.3Other descriptive nameTOLVAPTAN (OPC-41061)
    D.3.9.4EV Substance CodeSUB22755
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTolvaptan 50mg Granules
    D.3.2Product code OPC-41061
    D.3.4Pharmaceutical form Granules for oral suspension
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    Nasogastric use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTolvaptan
    D.3.9.1CAS number 150683-30-0
    D.3.9.2Current sponsor codeOPC-41061
    D.3.9.3Other descriptive nameTOLVAPTAN (OPC-41061)
    D.3.9.4EV Substance CodeSUB22755
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Autosomal Recessive Polycystic Kidney Disease (ARPKD)
    Autosomal-rezessive polyzystische Nierenerkrankung (ARPKD)
    E.1.1.1Medical condition in easily understood language
    Genetic disorder that causes numerous cysts to grow in the kidneys.
    Genetische Störung, bei der zahlreiche Zysten in den Nieren wachsen
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10036047
    E.1.2Term Polycystic kidney, autosomal recessive
    E.1.2System Organ Class 100000004850
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the safety of tolvaptan in pediatric subjects with ARPKD
    Beurteilung der Sicherheit von Tolvaptan bei pädiatrischen Patienten mit ARPKD
    E.2.2Secondary objectives of the trial
    To evaluate the effect of tolvaptan on the need for RRT in pediatric subjects with ARPKD

    Beurteilung der Wirkung von Tolvaptan in Bezug auf die Notwendigkeit einer RRT bei pädiatrischen Patienten mit ARPKD
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    This is optional further research performed on the remainder of the samples collected during the study to understand the genetics of ARPKD
    E.3Principal inclusion criteria
    1. Male or female subjects between 28 days and less than 18 years of age, with clinical and imaging features that are consistent with a diagnosis of ARPKD with all the following characteristics: nephromegaly (> 2 standard deviations from age-appropriate standard via ultrasound); multiple renal cysts; and a history of oligohydramnios or anhydramnios in utero.
    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.
    1. Männliche oder weibliche Studienteilnehmer im Alter zwischen28 Tagen und <18 Jahren mit klinischen und bildgebenden Merkmalen, die mit der Diagnose einer ARPKD übereinstimmen. Folgende Merkmale sind: Nephromegalie (> 2 Standardabweichungen von der altersgemäßen Norm im Ultraschall); multiple Nierenzysten; und eine Vorgeschichte von Oligohydramnion oder Anhydramnion in der Gebärmutter.
    2. Eltern/Erziehungsberechtigte müssen in der Lage sein, vor Einleitung studienbezogener Maßnahmen eine schriftliche Einwilligungserklärung abzugeben, und müssen nach Einschätzung des leitenden Prüfers in der Lage sein, alle Anforderungen der Studie einzuhalten. Studienteilnehmer müssen in der Lage sein, ihre schriftliche Zustimmung zu geben, wenn sie nach den örtlichen Gesetzen alt genug sind, um ihre Zustimmung zu geben.


    E.4Principal 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
    1. Frühgeburt (≤ 32 Wochen Gestationsalter) für Kinder im Alter von 28 Tagen bis <12 Wochen
    2. Anurie oder Nierenersatztherapie (RRT), definiert als intermittierende oder kontinuierliche Hämodialyse, Peritonealdialyse, Hämofiltration, Hämodiafiltration oder Nierentransplantation in der Vorgeschichte.
    3. Hinweise auf syndromale Erkrankungen im Zusammenhang mit Nierenzysten (außer ARPKD)
    4. Abnorme Leberfunktionstest, einschließlich ALT und AST > 1,2 × ULN
    5. Vorliegen einer Splenomegalie oder portalen Hypertonie
    6. Eltern mit zystischer Nierenerkrankung
    7. Einnahme eines permanenten Diuretikums, das nach der Einführung von Tolvaptan nicht angepasst werden konnte.
    8. Flüssigkeitshaushalt kann nicht überwacht werden
    9. Durch den Prüfarzt festgestelltes Ungleichgewicht von Natrium, Kalium und Elektrolyten
    10. Durch den Prüfarzt festgestelltes Risiko für signifikante Hypovolämie (z. B. bei Personen, die keinen freien Zugang zu Wasser haben [Unfähigkeit, auf Durst zu reagieren, abhängig vom Alter], ohne angemessene Flüssigkeitsüberwachung
    11. Durch den Prüfarzt festgestellte klinisch signifikante Anämie
    12. Thrombozytenzahl < 50.000 µl
    13. Schwere systolische Dysfunktion, definiert als Ejektionsfraktion < 14 %
    14. Natriumspiegel im Serum < 130 mmol/l oder >145 mmol/l (oder ULN eines lokalen Labors, je nachdem welcher Wert niedriger ist)
    15. Einnahme anderer experimenteller Medikamente
    16. Erforderliche Atmungsunterstützung mit Beatmungsgerät
    17. Einnahme von Medikamenten, die bekanntermaßen CYP3A4 induzieren
    18. Aktive Infektion einschließlich Virusinfektion, die eine Therapie erforderlich macht, welche die IMP-Dosisgabe beeinträchtigen würde
    19. Frauen, die stillen oder vor Einnahme des IMP einen positiven Schwangerschaftstest haben.
    20. Patienten mit einer Vorgeschichte von missbräuchlicher Substanzeinnahme innerhalb der letzten 6 Monate (abhängig vom Alter).
    21. Patienten mit einer Blasenfunktionsstörung und/oder Schwierigkeiten bei der Blasenentleerung.
    22. Patienten, die einen Vasopressin-Agonisten (z. B. Desmopressin) einnehmen.
    23. Patienten mit einer Vorgeschichte anhaltender Nicht-Compliance bei einer antihypertensiven oder anderen wichtigen medizinischen Therapie
    24. Patienten, die Begleiterkrankungen haben oder Medikamente einnehmen, die die Endpunktbewertung beeinträchtigen können, einschließlich der Einnahme von zugelassenen (am Markt erhältlichen) Therapien zur Behandlung von PKD-Zysten wie Tolvaptan, Vasopressin-Antagonisten, Antisense-RNA-Therapien, Rapamycin, Sirolimus, Everolimus oder Somatostatin-Analoga (wie Octreotid, Sandostatin)
    25. Patienten, die nicht bereit sind abstinent zu bleiben oder eine Kombination aus zwei der folgenden hochwirksamen Verhütungsmethoden anzuwenden. DIese sind anzuwenden mindestens 28 Tage vor der ersten Studienmedikamenten-Dosis, während der Studie (einschließlich der Unterbrechung der Studienmedikamenten-Dosis) und mindestens 30 Tage nach der letzten Dosis des Studienmedikamentes.
    Barrieremethode zur Empfängnisverhütung: Kondome mit oder ohne Spermizid, Diaphragma oder Portiokappe mit Spermizid, Intrauterinpessar, hormonelle Verhütungsmittel die mit einer Hemmung des Eisprungs verbunden sind.
    26. Eine Lebertransplantation wurde durchgeführt oder ist geplant
    27. Cholangitis in der Anamnese innerhalb der letzten 6 Monate
    28. Befunde, die auf eine klinisch signifikante portale Hypertension hindeuten (z. B. Varizen, Varizenblutungen, Blutungen, Hypersplenismus mit Thrombozytopenie




    E.5 End points
    E.5.1Primary 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+
    Sicherheitsbewertungen, die durch deskriptive Statistiken zusammengefasst werden, mit folgenden Endpunkten:
    - Unerwünschte Ereignisse
    - Vitalparameter
    - Klinische Laboruntersuchungen
    - Erhöhte Serum-Transaminase-Werte nach Häufigkeit (2 ×, 3 ×, 5 × und 10 × ULN), Zeit bis zum Eintreten, Zeit bis zum Spitzenwert, Zeit bis zum Abklingen der Wirkung (< 3 ×, 2 × oder 1 × ULN), Reaktion auf De-Challenge und Re-Challenge und Häufigkeit der Progression zu den Kriterien von Hy’s Gesetz (ALT oder AST > 3 × ULN und BT > 2 × ULN ohne alkalische Phosphatase 2 × ULN)
    Änderung vom Ausgangswert bei SNa+

    E.5.1.1Timepoint(s) of evaluation of this end point
    Months 1, 6, 12, and 18
    Monat 1, 6, 12 und 18
    E.5.2Secondary 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
    Jährliche Änderungsrate der eGFR (eGFR Schwartz-Formel = 0,413 × Größe [oder Länge in cm] / Serumkreatinin mg/dl) von Baseline bis zur Nachbehandlung nach 18 Monaten der Behandlung
    -Veränderung von eGFR-Baseline (eGFR Schwartz-Formel = 0,413 × Größe [oder Länge in cm] / Serumkreatinin mg/dl) während der Behandlung im Monat 1, 6, 12 und 18
    -Zeit bis Beginn der RRT
    -Prozentsatz der Studienteilnehmer, die RRT erhalten


    E.5.2.1Timepoint(s) of evaluation of this end point
    Months 1, 6, 12, and 18
    Monat 1, 6, 12 und 18
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    United States
    France
    Poland
    Spain
    Czechia
    Germany
    Italy
    Belgium
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The overall trial duration is considered from the time the first ICF is signed to the final subject assessment and is expected to be approximately 3.5 years. All subjects may be followed for 18 months after the first dose of IMP, regardless of continued compliance with taking IMP.
    Insgesamt gilt der Zeitraum ab Unterzeichnung der ersten Einwilligungserklärung bis zur abschließenden Beurteilung der Studienteilnehmer als Studiendauer. Er beträgt voraussichtlich ca. 3,5 Jahre. Alle Studienteilnehmer können in den 18 Monaten nach der ersten Dosis des Prüfarzneimittels beobachtet werden, unabhängig von der weiteren Compliance bei der Einnahme des Prüfarzneimittels.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 10
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 2
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 3
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 5
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    at least 10 male or female subjects, aged 28 days to less than 18 years at time of enrollment, with a clinical diagnosis of ARPKD
    mindestens 10 männliche oder weibliche Patienten im Alter von 28 Tagen bis<18 Jahren zum Zeitpunkt des enrollments, mit einer klinischen Diagnose von ARPKD
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 6
    F.4.2.2In the whole clinical trial 10
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    The subjects will be treated with standard of care by their healthcare provider and/or will have the option to enroll in an expanded access program to continue to receive tolvaptan as determined by the local regulations and at the sponsor's discretion dependant on safety data.
    N/A
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-12-03
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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