Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43883   clinical trials with a EudraCT protocol, of which   7296   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools

    < Back to search results

    Print Download

    EudraCT Number:2019-004959-36
    Sponsor's Protocol Code Number:446002504
    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:2020-09-30
    Trial results
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2019-004959-36
    A.3Full title of the trial
    A proof of concept phase II study with the PDE-4 inhibitor roflumilast in patients with mild cognitive impairment (MCI).
    Fase 2 studie met de PDE4 inhibitor roflumilast in patiënten met milde cognitieve stoornissen (MCI).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Cognitive effects of roflumilast in patients with mild cognitive impairment (MCI).
    Cognitieve effecten van roflumilast bij patiënten met milde cognitieve stoornissen (MCI).
    A.3.2Name or abbreviated title of the trial where available
    Cognitive effects of roflumilast in MCI patients
    Cognitieve effecten van roflumilast in MCI patiënten
    A.4.1Sponsor's protocol code number446002504
    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 SponsorZonMw
    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 supportZonMv (the Netherlands Organization for Health Research and Development)
    B.4.1Name of organisation providing supportMaastricht University
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMaastricht University
    B.5.2Functional name of contact pointPrinicipal Investigator
    B.5.3 Address:
    B.5.3.1Street AddressUniversiteitssingel 50
    B.5.3.2Town/ cityMaastricht
    B.5.3.3Post code6200 MD
    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. name Daxas (EU)
    D. of the Marketing Authorisation holderAstraZeneca AB
    D.2.1.2Country which granted the Marketing AuthorisationBelgium
    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, soft
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    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. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. 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
    Mild Cognitive Impairment (MCI)
    Milde Cognitieve Stoornissen (MCI)
    E.1.1.1Medical condition in easily understood language
    Mild Cognitive Impairment
    Milde Cognitieve Stoornissen
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Psychological processes [F02]
    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 of the proposed proof-of-concept phase II study is to validate the effect of roflumilast on episodic memory, namely the verbal learning test (VLT) immediate and delayed recall (15 words), in MCI patients after chronic roflumilast treatment of 24 weeks.
    E.2.2Secondary objectives of the trial
    Our secondary objective is multifaceted. Other cognitive domains will be measured using:
    - the Letter Digit Substitution test ;
    - the Trail-making test (TMT);
    - the Pattern Separation Task;
    - the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) (minus the word recall task and the word recognition task),
    - VLT recognition;
    - and the Mini-Mental State Examination (MMSE).

    Additionally, wellbeing and quality of life questionnaires regarding the participant, namely EuroQol, quality of life AD (QoLAD) and Hospital Anxiety and Depression Scale (HADS), and his/her informal caregiver, namely the Neuropsychiatric Inventory (NPI) and the Alzheimer’s Disease Cooperative Study Activities of Daily Living Scale (ADCS ADL-MCI), are included to gain more insight in the relation between (improved) cognition, quality of life, mood and emotion.

    We do take tau measurement from tears in to our measurements, as well as the conversion from MCI to AD (yes/no).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - 50 to 90 years of age;
    - willingness (both the participant and informal caregiver) to sign an IC;
    - body mass index (BMI) between 18.5 and 30;
    - MMSE of 20 or higher;
    - MCI due to AD diagnosis which includes either increased cerebrospinal fluid (CSF) amyloid-beta marker and/or a positive biomarker of neuronal injury i.e. magnetic resonance imaging (MRI) scan including measurements of decreased hippocampal volume or medial temporal atrophy by volumetric measures or visual rating);
    - memory performance on the delayed recall in the 15 words VLT of 1-2 standard deviation(s) (SD) below the average.

    E.4Principal exclusion criteria
    A potential subject who meets any of the following criteria will be excluded from participating in this study: receiving current irradiation, HIV positive, Hepatitis B/C, Normal Pressure Hydrocephalus (NPH), Morbus Huntington, Parkinson's disease, recent Transient Ischemic Attack (TIA) or Cerebrovascular Accident (CVA) (< 2 years), TIA/CVA followed by cognitive decline (within 3 months), COPD, history of schizophrenia, bipolar disorder or psychotic symptoms not otherwise specified or previous treatment for these diseases (lifetime), current affective disorder (i.e. anxiety or major depression), cognitive problems due to alcohol abuse, brain tumor, epilepsy, encephalitis or lack of capacity to consent to participation. Other exclusion criteria are current treatment with (or illicit use of) centrally acting beta-blockers, cannabis, opiates, benzodiazepines, Methylenedioxymethamphetamine (MDMA) and cocaine. Roflumilast is contraindicated in patients with moderate to severe liver impairment, accordingly patients with moderate or major liver impairments will be excluded (e.g. Child-Pugh B and C). Use of medication showing strong inhibition of either CYP3A4 (e.g. clarithromycin and other similar antihistamines) or CYP1A2 (e.g. fluvoxamine, ciprofloxacin and other fluoroquinolones) is also an exclusion criterion because of interference with roflumilast metabolism resulting in reduced therapeutic effectiveness of roflumilast. Individuals with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption will be excluded, as both the placebo and roflumilast contain lactose monohydrate. Additionally, during the period of the present study, participants are not allowed to participate in other drug trials. Lastly, if a participant does not have the possibility to be accompanied at every test session by the same informal caregiver they will be excluded.
    E.5 End points
    E.5.1Primary end point(s)
    Expected increase in verbal learning task (VLT) recall in words in the immediate and in the delayed condition (15 words) at 24 weeks.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at 12 weeks of chronic intake of Roflumilast
    at 24 weeks of chronic intake of Roflumilast
    2 weeks follow up post 24 weeks of chronic intake of Roflumilast
    E.5.2Secondary end point(s)
    Expected increased recognition score on the VLT. In addition, a decrease in the reaction time (RT) in the Trail-making test, LDST, as well as a decrease in the amount of errors in the LDST is expected. We expect an improvement in scores in the MMSE and the ADAS-Cog, as well as an increase in score regarding the wellbeing, mood and quality of life questionnaires for both the patient and the informal caregiver.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Acute (except MMSE)
    at 12 weeks of chronic intake of Roflumilast
    at 24 weeks of chronic intake of Roflumilast
    2 weeks follow up post 24 weeks of chronic intake of Roflumilast
    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 No
    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. 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 Yes
    E. trial design description
    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 trial3
    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
    Premature termination is indicated only when a reoccurring serious adverse effect (SAE) has led to unblinding of individual randomised subject codes and is considered to be a suspected unsuspected serious adverse reaction (SUSAR). All subjects that received roflumilast will be informed as will the accredited METC and the Competent Authority as indicated by GCP and national guidelines. Available data will be analysed.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    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: 81
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 81
    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 state81
    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)
    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 Decision2020-09-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-09-10
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands