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    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2021-001833-38
    Sponsor's Protocol Code Number:77347
    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:2023-03-31
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2021-001833-38
    A.3Full title of the trial
    The Dutch Parkinson GBA Ambroxol trial (DUPARG-AMBROXOL):
    A randomised, double-blind, placebo-controlled, single-center trial with Ambroxol in Parkinson patients with a GBA mutation.
    De Nederlandse Trial met Ambroxol bij Parkinson patiënten met een GBA mutatie (DUPARG-AMBROXOL):
    Een gerandomiseerde, dubbel-blinde, placebo-gecontroleerde, single-center trial met Ambroxol bij Parkinson patiënten met een GBA mutatie.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The Dutch Parkinson GBA Ambroxol trial
    De Nederlandse Trial met Ambroxol bij Parkinson patiënten met een GBA mutatie
    A.3.2Name or abbreviated title of the trial where available
    DUPARG-AMBROXOL
    DUPARG-AMBROXOL
    A.4.1Sponsor's protocol code number77347
    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 SponsorUniversity Medical Center Groningen
    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 supportUniversity Medical Center Groningen
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Medical Center Groningen
    B.5.2Functional name of contact pointUniversity Medical Center Groningen
    B.5.3 Address:
    B.5.3.1Street AddressHanzeplein 1
    B.5.3.2Town/ cityGroningen
    B.5.3.3Post code9713 GZ
    B.5.3.4CountryNetherlands
    B.5.4Telephone number00310503615639
    B.5.5Fax number00310503615639
    B.5.6E-mailo.siemeling@umcg.nl
    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 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 nameAmbroxol hydrochloride
    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 INNAmbroxol hydrochloride
    D.3.9.1CAS number 15942-05-9
    D.3.9.4EV Substance CodeSUB00427MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1800
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Parkinson's disease with a GBA1 mutation
    Ziekte van Parkinson met een GBA1 mutatie
    E.1.1.1Medical condition in easily understood language
    Parkinson's disease
    Ziekte van Parkinson
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective is to compare the effectiveness of ambroxol versus placebo on the MDS-UPDRS part III motor sub-score in the “practically defined OFF-medication state” in patients with moderate PD, carrying a GBA mutation. The hypothesis is that ambroxol will be associated with reduced MDS-UPDRS part III scores at the 60 week time-point after a 12 week washout period.
    Het primaire doel is om de werkzaamheid van Ambroxol versus placebo te vergelijken op de MDS-UPDRS deel III, als motorische subscore in de "praktische gedefinieerde OFF-medicatie toestand" bij patiënten ziekte van Parkinson en een GBA-mutatie. De hypothese is dat Ambroxol geassocieerd zal zijn met verminderde MDS-UPDRS III scores op het tijdstip van 60 weken na een wash-out periode van 12 weken.
    E.2.2Secondary objectives of the trial
    Secondary objectives will compare the differences at 60 weeks between the ambroxol and placebo trial arms with respect to:
    -Safety and tolerability
    -Participant’s prediction of their treatment (ambroxol or placebo) to asses adequate blinding
    -Glucocerebrosidase (GCase) activity in blood mononuclear cells by measuring sphingolipids
    -Striatal F-DOPA uptake as measured by [18] F-DOPA PET scan
    -Relationship between resting-state functional and structural connectivity as measured by MR imaging and dopaminergic innervation (PET scan)
    -Integrity of the nigrostriatal fibers, connecting the substantia nigra and putamen, using diffusion tensor imaging (DTI) tractography
    -Quality of Life (PDQ-39 questionnaire)
    -Non Motor Symptoms (NMSS scale)
    -Cognition, using the Montreal Cognitive Assessment (MoCA)
    -Levodopa dose (LED, Ldopa Equivalent Dose)
    Bepalen van het verschil na 60 weken tussen de Ambroxol en placebo behandelde groep in:
    - veiligheid en verdraagzaamheid in de bestudeerde populatie
    - Voorspelling van de deelnemer van hun behandeling (ambroxol of placebo) om adequate verblinding te beoordelen
    - de GCase-activiteit van patiënten met ZvP met een GBA mutatie door middel van het bepalen van sfingolipiden
    - striatale F-DOPA opname gemeten met [18]F-DOPA PET-scan
    - Relatie tussen functionele en structurele connectiviteit in rusttoestand zoals gemeten door MR-beeldvorming en dopaminerge innervatie (PET-scan)
    - Integriteit van de nigrostriatale vezels, die de substantia nigra en het putamen verbinden, met behulp van diffusie tensor imaging (DTI) tractografie
    - kwaliteit van leven (PDQ-39 vragenlijst)
    - non-motor symptomen (NMSS schaal)
    - Cognitie (MoCA)
    - Levodopa equivalente dosering (LED)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    In order to be eligible to participate in this study, a subject must meet all of the following criteria:
    -Diagnosis of Parkinson’s disease, according to Movement Disorders Society (MDS) criteria <10 years
    -PD patients carrying a GBA1 mutation
    -Able to write written informed consent, understanding study protocol and perform protocol related actions
    -Willing and able to self-administer oral ambroxol medication
    Om in aanmerking te komen voor deelname aan dit onderzoek, moet een proefpersoon aan alle volgende criteria voldoen:
    - Diagnose ziekte van Parkinson volgens de Movement Disorders Society (MDS) criteria <10 jaar
    - Patiënten met de ziekte van Parkinson en ene GBA1 mutatie
    - Bereid zijn om mee te werken en informed consent te tekenen, het onderzoeksprotocol te begrijpen en protocolgerelateerde acties uit te voeren
    - Bereid en in staat om zelf orale ambroxol medicatie toe te dienen
    E.4Principal exclusion criteria
    A potential subject who meets any of the following criteria will be excluded from participation in this study:
    -The refusal to be informed about an unforeseen clinical finding
    -Use of an implanted Deep Brain Stimulation (DBS) system
    -Confirmed dysphagia that would preclude self-administration of ambroxol or placebo tablets
    -History of known sensitivity to the study medication
    -Pregnant or breastfeeding women
    -Participants of child bearing potential that would not use adequate birth control while participating in the study
    -MRI incompatible implants in the body
    -Any clinically significant or unstable medical or surgical condition that in the opinion of the principal investigator may put the participant at risk when participating in the study or may influence the results of the study or affect the participant’s ability to take part in the study, as determined by medical history, physical examinations, electrocardiogram (ECG), or laboratory tests. Such conditions may include:
    1. Impaired renal function
    2. Moderate/severe hepatic impairment
    3. A major cardiovascular event (e.g. myocardial infarction, acute coronary syndrome, decompensated congestive heart failure, pulmonary embolism, coronary revascularisation that occurred within 6 months prior to the screening visit.)
    Een potentiële proefpersoon die aan een van de volgende criteria voldoet, wordt uitgesloten van deelname aan dit onderzoek:
    - De weigering om geïnformeerd te worden over een onvoorziene klinische bevinding
    - Gebruik van een geïmplanteerd diepebreinstimulatie (DBS)-systeem
    - Bevestigde dysfagie die zelftoediening van ambroxol of placebotabletten zou uitsluiten
    - Geschiedenis van bekende gevoeligheid voor de onderzoeksmedicatie
    - Zwangere vrouwen of vrouwen die borstvoeding geven
    - Deelnemers in de vruchtbare leeftijd die geen adequate anticonceptie zouden gebruiken tijdens hun deelname aan het onderzoek
    - MRI-incompatibele implantaten in het lichaam
    - Elke klinisch significante of onstabiele medische of chirurgische aandoening die naar het oordeel van de hoofdonderzoeker de deelnemer in gevaar kan brengen bij deelname aan de studie of die de resultaten van de studie kan beïnvloeden of het vermogen van de deelnemer om deel te nemen aan de studie, zoals bepaald door medische geschiedenis, lichamelijk onderzoek, elektrocardiogram (ECG) of laboratoriumtests. Dergelijke voorwaarden kunnen zijn:
    1. Verminderde nierfunctie
    2. Matige/ernstige leverfunctiestoornis
    3. Een groot cardiovasculair voorval (bijv. myocardinfarct, acuut coronair syndroom, gedecompenseerd congestief hartfalen, longembolie, coronaire revascularisatie die optrad binnen 6 maanden voorafgaand aan het screeningsbezoek.)
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the comparison of MDS-UPDRS part III motor subscale in the practically defined OFF medication state at 60 weeks after a 12 week washout period.
    Het primaire eindpunt is het verschil tussen de MDS-UPDRS deel III motorische subschaal in de praktisch gedefinieerde OFF medicatiestaat na 60 weken, na een wash-out periode van 12 weken.
    E.5.1.1Timepoint(s) of evaluation of this end point
    60 weeks
    60 weken
    E.5.2Secondary end point(s)
    Secondary endpoints are:
    -Safety and tolerability by examine adverse events
    -F-DOPA PET
    -MRI
    -Montreal Cognitive Assessment (MoCA)
    -Non-Motor Symptoms scale (NMSS)
    -Parkinson’s Disease 39 item Quality of life questionnaire (PDQ-39)
    -GCase activity by measuring sphhingolipids using peripheral blood mononuclear cells (PBMCs) and blood plasma
    Secundaire doelstellingen zijn:
    Bepalen van het verschil na 60 weken tussen de Ambroxol en placebo behandelde groep in:
    - veiligheid en verdraagzaamheid in de bestudeerde populatie
    - Voorspelling van de deelnemer van hun behandeling (ambroxol of placebo) om adequate verblinding te beoordelen
    - de GCase-activiteit van patiënten met ZvP met een GBA mutatie
    - striatale F-DOPA opname gemeten met [18]F-DOPA PET-scan
    - Relatie tussen functionele en structurele connectiviteit in rusttoestand zoals gemeten door MR-beeldvorming en dopaminerge innervatie (PET-scan)
    - Integriteit van de nigrostriatale vezels, die de substantia nigra en het putamen verbinden, met behulp van diffusie tensor imaging (DTI) tractografie
    - kwaliteit van leven (PDQ-39 vragenlijst)
    - non-motor symptomen (NMSS schaal)
    - Cognitie (MoCA)
    - Levodopa equivalente dosering (LED)
    E.5.2.1Timepoint(s) of evaluation of this end point
    at 60 weeks after 12 weeks wash-out period.
    Na 60 weken na 12 weken wash-out periode.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 50
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state80
    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)
    NONE
    Geen.
    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 Decision2023-04-20
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-03-13
    P. End of Trial
    P.End of Trial StatusOngoing
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