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    The EU Clinical Trials Register currently displays   43233   clinical trials with a EudraCT protocol, of which   7153   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:2004-001162-40
    Sponsor's Protocol Code Number:E2020-A001-233
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-01-20
    Trial results View 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 ConcernedSpain - AEMPS
    A.2EudraCT number2004-001162-40
    A.3Full title of the trial
    An 18-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of donepezil HCl (E2020) in patients with CADASIL who have cognitive impairment.
    A.3.2Name or abbreviated title of the trial where available
    Donepezil HCl in CADASIL
    A.4.1Sponsor's protocol code numberE2020-A001-233
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorEisai Ltd
    B.1.3.4CountryUnited Kingdom
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Information not present in EudraCT
    D.2.1.1.1Trade name Aricept
    D.2.1.1.2Name of the Marketing Authorisation holderEisai Ltd
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 nameAricept
    D.3.2Product code E2020
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNdonepezil hydrochloride
    D.3.9.1CAS number 120011-70-3
    D.3.9.2Current sponsor codeE2020
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    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 placeboFilm-coated tablet
    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
    Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).


    CADASIL is a genetic disorder representing a minority of the patients who develop vascular dementia.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 7.0
    E.1.2Level PT
    E.1.2Classification code 10057678
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to determine whether donepezil HCl confers cognitive benefit in patients with CADASIL who have cognitive impairment.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are to evaluate the safety and tolerability of donepezil HCl in patients with CADASIL who have cognitive impairment.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    1) Age range: Adult patients, 25 to 70 years of age inclusive.
    2) Gender distribution: men and women. Women of childbearing potential (<1 year post menopausal) must be practicing effective contraception and have a negative serum β-HCG at Screening. Pregnant and/or lactating females are excluded. Patients who become pregnant during the study will be discontinued.
    3) Diagnostic evidence of CADASIL either by (1) identification of a NOTCH3 mutation (excluding polymorphisms) or (2) presence of typical deposits on an electron microscopy of a skin biopsy.
    4) Cognitive impairment: (1) Subjects or their study partners must give a description of cognitive problems and one of the following: (2a) MMSE score of 10 to 27 (inclusive) or (2b) Trails B score, 1.5 standard deviations below the mean after adjustment for age and education.
    5) Head MRI: Evidence of disease consistent with CADASIL, and no evidence of another disease, which might account for cognitive impairment or dementia (as judged by the Investigator/physician at the site). (The latter may be determined with a CT head for eligibility purposes. The MRI would still be needed.) Must be obtained within 6 months of the Screening/Baseline visit. If no such head MRI had been previously obtained, a head MRI will be obtained as part of Screening/Baseline after all other inclusion and exclusion criteria (except clinical laboratory determinations) are satisfied. Patients in whom an MRI is contraindicated can have a CT instead, however, MRI is the preferred modality.
    6) Race and ethnicity: any race and ethnic group.
    7) Health: generally healthy, ambulatory or ambulatory-aided (i.e., walker, cane or wheelchair) outpatient. Speech, motor function, comprehension, and corrected vision and hearing must be sufficient for compliance with all testing procedures.
    8) Clinical laboratory values must be within normal limits, or if abnormal, must be judged clinically insignificant by the Investigator/physician.
    9) Patients with vitamin B12 deficiency who are on a stable dose of medication for at least 12 weeks prior to Screening/Baseline and who have normal serum B12 levels at Screening/Baseline will be eligible. Patient who might otherwise have been eligible can be re-screened when they meet this criterion. This stable dose of vitamin B12 must be maintained throughout the study.
    10) Patients with hypothyroidism or hyperthyroidism who are on a stable dose of medication for at least 12 weeks prior to Screening, have a normal TSH and free T4 at screening, and are considered euthyroid will be eligible. Patient who might otherwise have been eligible can be re-screened when they meet this criterion. This stable dose must be maintained throughout the study.
    11) Patients must have a reliable study partner who has regular contact with the patient (e.g, an average of 4 or more contacts per week), can observe for possible adverse events, and can accompany the patient to all visits.
    12) Patients with a history of hypertension, cardiac disease, diabetes, or peripheral vascular disease, may be enrolled in the study provided that the following standards are met. Hypertension must be medication controlled (sitting SBP < 175, sitting DBP < 100 mm Hg) and cardiac disease (e.g. angina pectoris, congestive heart failure, right bundle branch block, or arrhythmias) is stable on appropriate medication for 12 weeks prior to Screening. Peripheral vascular disease must have been stable for 12 weeks prior to Screening. No elective surgical procedures should be planned during the course of the study (e.g. hernia repair and bunion removal). Patient with diabetes must be stable as demonstrated by an HbA1c of ≤ 8.0% or a random serum glucose value of ≤ 170 mg/dL.
    13) All patients with CADASIL are at risk for stroke / TIA and may be enrolled in the study provided that no new strokes have been diagnosed or identified to have occurred within the three months prior to Screening. Patient who might otherwise be eligible can be screened 12 weeks after the stroke. Patients with TIAs are eligible without a waiting period. Patients who are already enrolled will continue in the study as assessed by the Investigator/physician.
    14) Patients with CADASIL may suffer depression. Such patients are eligible for enrollment if they are stable on medication for 12 weeks and have an MADRS score < 20. Patients with an MADRS score ≥ 20 may be re-screened after 12 weeks on a stable dose of medication. This stable dose must be maintained throughout the study.
    15) Minor medical conditions must be stable before study enrollment
    16) Patient who are taking Gingko Biloba or vitamin E and have been taking stable doses of these compounds for 8 weeks are allowed in the study. This stable dose must be maintained throughout the study.
    E.4Principal exclusion criteria
    1) Neurological disorders affecting cognition or the ability to assess it that are not associated with CADASIL, such as Alzheimer’s Disease, Parkinson’s disease, normal pressure hydrocephalus, idiopathic seizure disorders, multiple sclerosis, cerebral vasculitis or infections of the central nervous system, subdural hematoma, as well as Human Immunodeficiency Virus (HIV) disease, a history of significant head trauma followed by persistent neurological deficits, sleep disorders affecting level of consciousness, or known structural brain abnormalities.
    2) Psychiatric disorders affecting the ability to assess cognition that are not typically associated with CADASIL, such as schizophrenia.
    3) Active drug or alcohol abuse or dependence in ≤ 5 years by DSM-IV criteria.
    4) Any active or clinically significant conditions affecting absorption, distribution, or metabolism of the study medication (e.g, inflammatory bowel disease, hepatic disease, or severe lactose intolerance).
    5) Uncontrolled hypertension (sitting systolic ≥ 175 mmHg and/or diastolic ≥ 100 mmHg) as assessed by the Investigator regardless of whether the patient is taking antihypertensive medication.
    6) Evidence of clinically significant, active gastrointestinal, renal, hepatic, respiratory, infectious, endocrine, or cardiovascular system disease. A patient so excluded, who subsequently becomes stable for 4 weeks, may become eligible for enrollment if all other criteria in Sections 8.2 and 8.3 are met. Patients with left bundle branch block are excluded.
    7) History of malignant neoplasms (does not include basal or squamous cell carcinoma of the skin) treated within 2 years prior to study entry, current evidence of malignant neoplasm, or recurrent or metastatic disease.
    8) Women who are pregnant or breast-feeding.
    9) Patients and/or study partners who are unwilling or unable to fulfill the requirements of the study.
    10) Known hypersensitivity to cholinesterase inhibitors or piperidine-containing drug.
    11) Use of any unapproved prior or concomitant medications as defined in Sections 8.4 and Appendix 2 (This list is not exhaustive. If there area are questions, please ask the Medical Monitor.)
    12) Any condition that would make the patient or study partner, in the opinion of the Investigator, unsuitable for the study.
    13) Involvement in any other investigational trial in the preceding 12 weeks or likely involvement in any other investigational study drug trial during the course of this study. Prior to enrollment the study director must approve involvement in investigational trials that do not involve a study drug.
    14) Patients with changes in doses of concomitant medication, not otherwise described, within the 6 weeks prior to enrollment.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint will be based on the V-ADAS-Cog score at 18 weeks or Early Termination. Secondary endpoints include evaluation of ADAS-Cog, Mini-Mental State Exam (MMSE), Trail Making Test (TMT), Stroop Test, EXIT25, CLOX, Disability Assessment for Dementia (DAD), and correlation of MRI findings with treatment effect in these patients. Further analyses will evaluate all of these endpoints in the subset of patients with NINDS-AIREN defined vascular dementia. Parameters will be measured at the Screening/Baseline visit, during, and at the end of the study. Safety and tolerability will be collected from adverse events, medical history, physical and neurological examination, EKGs and clinical laboratory tests.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Information not present in EudraCT
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) Information not present in EudraCT
    E.7.4Therapeutic use (Phase IV) Information not present in EudraCT
    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 Yes
    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.8.3 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.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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 end of the trial is the last visit of the last subject undergoing the trial.
    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 months7
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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
    Consent can be given with the advice of a legal representative.
    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.4.2.2In the whole clinical trial 150
    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 Decision2005-03-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-02-01
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2006-10-20
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