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    Summary
    EudraCT Number:2013-002457-30
    Sponsor's Protocol Code Number:13.0099
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2013-07-01
    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 ConcernedUK - MHRA
    A.2EudraCT number2013-002457-30
    A.3Full title of the trial
    An open label randomised controlled trial investigating the effect of donepezil on regional cerebral blood flow in adults with aneurysmal subarachnoid haemorrhage.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Donepezil for the prevention of further delayed stroke following brain bleeding
    A.3.2Name or abbreviated title of the trial where available
    Donepezil in Aneurysmal Subarachnoid Haemorrhage (DASH) Trial
    A.4.1Sponsor's protocol code number13.0099
    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 SponsorSt George's University of London
    B.1.3.4CountryUnited Kingdom
    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 supportNeuroscience Research Foundation
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSt George's Hospital NHS Trust
    B.5.2Functional name of contact pointDr Jeremy B Madigan
    B.5.3 Address:
    B.5.3.1Street AddressBlackshaw Road
    B.5.3.2Town/ cityLondon
    B.5.3.3Post codeSW17 0QT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number02087254481
    B.5.6E-mailjeremy.madigan@nhs.net
    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 Aricept Evess
    D.2.1.1.2Name of the Marketing Authorisation holderEisai Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 Evess
    D.3.4Pharmaceutical form Dispersible tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPNasogastric use (Noncurrent)
    Oral 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.3.9.4EV Substance CodeAS1
    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) 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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Aneurysmal subarachnoid haemorrhage
    Cerebral vasospasm
    Ischaemic stroke
    E.1.1.1Medical condition in easily understood language
    Stroke/permanent disability caused by reduced reduced blood flow to the brain, which is due to the narrowing of brain blood vessels after a specific type of brain bleeding (subarachnoid hemorrhage).
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.0
    E.1.2Level LLT
    E.1.2Classification code 10047164
    E.1.2Term Vasospasm cerebral
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.0
    E.1.2Level PT
    E.1.2Classification code 10061256
    E.1.2Term Ischaemic stroke
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.0
    E.1.2Level LLT
    E.1.2Classification code 10055845
    E.1.2Term Haemorrhage subarachnoid
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Does donepezil improve brain blood flow after brain bleeding from aneurysms (subarachnoid haemorrhage)?
    E.2.2Secondary objectives of the trial
    Is donepezil safe and well tolerated in patients with acute brain bleeding (subarachnoid haemorrhage)?
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients aged 18-85 admitted to St George's Hospital neurosurgical service with confirmed aneurysmal subarachnoid haemorrhage (brain bleeding from an aneurysm).
    2. Amount of blood: Fisher score = 2 or greater (blood load on CT scan)
    3. Able to be enroled within 12-72 hours of brain bleeding symptom onset.
    4. Index aneurysm suitable for endovascular occlusion (coiling)
    E.4Principal exclusion criteria
    1. Allergy to donepezil or other piperidine derivatives.
    2. Pregnancy.
    3. Lactating or breast feeding women
    4. Male or female participants that are unwilling to use an effective method of birth control (hormonal or barrier method of birth control; abstinence from time consent is signed until 6 weeks after the last dose of Donepezil
    5. Known dementia.
    6. Severe hepatic impairment (Child-Pugh Class C)
    7. Patients with ‘sick sinus syndrome’ or other supraventricular cardiac conduction conditions such as sino-atrial or atrioventricular block.
    8. Patients with a history of brittle asthma or obstructive pulmonary disease, requiring regular steroid (inhalers or tablet) for control.
    E.5 End points
    E.5.1Primary end point(s)
    Changes in regional cerebral blood flow (mL/100g/min) measured by two Xenon CT perfusion scans, one performed before the administration of a loading dose of donepezil, and the other after this dose.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The first XeCT scan is performed under general anaesthetic immediately prior to the administration of the first dose of donepezil. It is expected that this would occur within the first 24 hours after enrolment. The second XeCT scan would be performed as soon as possible after the treatment of the participant's aneurysm (but not less than 3 hours after the first XeCT scan (timescale in protocol: 3-24h).
    E.5.2Secondary end point(s)
    1. Modified Rankin Score at 6 months.
    2. Evidence of brain infarction on imaging (CT or MRI) not related to aneurysm occlusion treatment.
    3. Delayed clinical neurological deficits.
    4. Number of hospital days.
    5. Need for endovascular treatment of large vessel spasm
    E.5.2.1Timepoint(s) of evaluation of this end point
    Modified Rankin Score - 6 months after admission.

    All other secondary outcomes would be evaluated during the participant's acute admission for subarachnoid haemorrhage (usually 1-4 weeks).
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    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 Yes
    E.8.1.3Single blind Yes
    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 Yes
    E.8.2.3.1Comparator description
    Standard Therapy
    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.8.4.1Number of sites anticipated in Member State concerned1
    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 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 years2
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days29
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days29
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 76
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 24
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2013-07-01. Yes
    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
    Patients suffering subarachnoid haemorrhage with WFNS clinical grade 2 or greater. Patients may lack capacity due to effect of haemorrhage on conscious level.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state100
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 0
    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 study drug would be administered daily for 21 days after the initial brain bleeding, since patients can develop vasospasm at any time within this period. After 21 days, the drug will be discontinued as the risk of vasospasm is minimal. After participation in the trial ends, there is no difference from the normal treatment.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-08-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-09-13
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2016-11-10
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