Kliniske forsøg Nct side

Summary
EudraCT Number:2021-006868-24
Sponsor's Protocol Code Number:UMCN-AKF-21.05
National Competent Authority:Netherlands - Competent Authority
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-06-24
Trial results
A. Protocol Information
A.1Member State ConcernedNetherlands - Competent Authority
A.2EudraCT number2021-006868-24
A.3Full title of the trial
Pharmacokinetics of fluconazole given orally or intravenously as prophylaxis or therapy to children and adolescents with invasive fungal infections (FOCUS)
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Exposure to fluconazole in children
A.3.2Name or abbreviated title of the trial where available
FOCUS
A.4.1Sponsor's protocol code numberUMCN-AKF-21.05
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorRadboud university medical centre
B.1.3.4CountryNetherlands
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportRadboud university medical center
B.4.2CountryNetherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationRadboud university medical center
B.5.2Functional name of contact pointRoger Brüggemann
B.5.3 Address:
B.5.3.1Street AddressGeert Grooteplein l0
B.5.3.2Town/ cityNijmegen
B.5.3.3Post code6525 GA
B.5.3.4CountryNetherlands
B.5.4Telephone number+31243616405
B.5.5Fax number+31243668755
B.5.6E-mail[email protected]
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.2.1.2Country which granted the Marketing AuthorisationNetherlands
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.3.4Pharmaceutical form Solution for infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFluconazole
D.3.9.1CAS number 86386-73-4
D.3.9.3Other descriptive nameFLUCONAZOLE
D.3.9.4EV Substance CodeSUB07674MIG
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number2
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.2.1.2Country which granted the Marketing AuthorisationNetherlands
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.3.4Pharmaceutical form Capsule
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 INNFluconazole
D.3.9.1CAS number 86386-73-4
D.3.9.3Other descriptive nameFLUCONAZOLE
D.3.9.4EV Substance CodeSUB07674MIG
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number400
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.2.1.2Country which granted the Marketing AuthorisationNetherlands
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.3.4Pharmaceutical form Powder for oral suspension
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 INNFluconazole
D.3.9.1CAS number 86386-73-4
D.3.9.3Other descriptive nameFLUCONAZOLE
D.3.9.4EV Substance CodeSUB07674MIG
D.3.10 Strength
D.3.10.1Concentration unit mg milligram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number400
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
Invasive fungal disease
E.1.1.1Medical condition in easily understood language
Infection with a fungus
E.1.1.2Therapeutic area Diseases [C] - Bacterial Infections and Mycoses [C01]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level PT
E.1.2Classification code 10017533
E.1.2Term Fungal infection
E.1.2System Organ Class 10021881 - Infections and infestations
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
To establish an improved fluconazole dosing regimen for children and adolescents.
E.2.2Secondary objectives of the trial
•To explore the role of renal function on the clearance of fluconazole.
•To explore the bioavailability of oral fluconazole versus intravenous fluconazole in paediatric patients.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
Inclusion criteria:
1.Subject is treated with fluconazole for prophylaxis or treatment of an invasive fungal infection;
2.Subject is 2 - 18 years of age on the day of the first fluconazole dosing;
3.Subject is managed with a central venous catheter or arterial line from which blood can be easily obtained.
E.4Principal exclusion criteria
Exclusion criteria:
1.Subject is managed by means of an extracorporeal clearance technique;
2.Subject has previously participated in this study.
E.5 End points
E.5.1Primary end point(s)
Since the primary objective of this study is to establish an improved fluconazole dosing regimen for paediatric and adolescent patients aged 2-18 years, we aim to describe fluconazole pharmacokinetics in this patient population by means of population pharmacokinetic (pop-PK) modelling. The pharmacokinetic parameters of the developed pop-PK model are among others, clearance (CL), volume of distribution (Vd) and exposure described by the area under the concentration-time curve (AUC). With the developed model, simulations will be performed to estimate the percentage of patients reaching the predefined PK target of AUC above 400 mg*h/L. We subsequently aim to establish an improved fluconazole dosing regimen for the studied population which will consist of a loading dose and a maintenance dose that will result in adequate fluconazole exposure in these patients.
E.5.1.1Timepoint(s) of evaluation of this end point
Day 2 of therapy (steady state).
E.5.2Secondary end point(s)
Exploratory objectives:
•To explore the role of renal function on the clearance of fluconazole.
•To explore the bioavailability of oral fluconazole versus intravenous fluconazole in paediatric patients.
E.5.2.1Timepoint(s) of evaluation of this end point
Day 2 of therapy (steady state)
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 No
E.6.5Efficacy No
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 No
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) No
E.7.4Therapeutic use (Phase IV) Yes
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.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned2
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA1
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
Germany
Netherlands
United Kingdom
E.8.7Trial has a data monitoring committee No
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
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years1
E.8.9.1In the Member State concerned months6
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years1
E.8.9.2In all countries concerned by the trial months6
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: 30
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) No
F.1.1.5Children (2-11years) Yes
F.1.1.5.1Number of subjects for this age range: 15
F.1.1.6Adolescents (12-17 years) Yes
F.1.1.6.1Number of subjects for this age range: 15
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
Since a real-life cohort of patients also includes those admitted to the ICU, some patients may be unconscious and thereby incapable of giving consent personally.
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state15
F.4.2 For a multinational trial
F.4.2.1In the EEA 22
F.4.2.2In the whole clinical trial 30
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)
No different treatment or care after completion of the trial
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 Decision2022-08-02
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-06-22
P. End of Trial
P.End of Trial StatusOngoing