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    Summary
    EudraCT Number:2004-001336-22
    Sponsor's Protocol Code Number:AX-PC-201
    National Competent Authority:Sweden - MPA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2004-08-04
    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 ConcernedSweden - MPA
    A.2EudraCT number2004-001336-22
    A.3Full title of the trial
    Effect of Phenserine Treatment on Amyloid in Brains of Patients with Mild Probable Alzheimer’s Disease as studied by Positron Emission Tomography (PET).
    A Randomised, three Months Double-Blind, Placebo-Controlled Pilot Study followed by a three Months Open-Label Treatment with Phenserine or Aricept.
    A.4.1Sponsor's protocol code numberAX-PC-201
    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 SponsorAxonyx Inc.
    B.1.3.4CountryUnited States
    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.2.5The 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 namephenserine tartrate
    D.3.4Pharmaceutical form 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.3.9.3Other descriptive namephenserine tartrate
    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 Yes
    D.3.11.13.1Other medicinal product typepharmaceutical (chemical product)
    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 placeboTablet
    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
    Alzheimer’s Disease (AD) is the most common disease leading to dementia and it affects approximately 4 to 8% of the population aged above 65 years. The disease incidence is closely correlated with increasing age and it doubles within every 5 years time period of increasing age.Optimal treatment would slow down or even stop the progression of disease, to maintain the independence of the patient by improving his every-day competency.
    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 objective of this phase IIb pilot study is to assess the safety of PT treatment and the effects of this drug on cognitive performance, brain metabolic activity as well as on APP metabolism in comparison to Placebo/active drug treatment in patients suffering from Alzheimer’s Disease. Special attention will be focused on PT effects on brain amyloid load and brain glucose metabolism.

    Primary:
    Placebo-controlled comparison of the efficacy of Phenserine-tartrate (PT,15 mg BID) based on the following end-points:

    • Cerebral Glucose metabolism using Positron Emission Tomography (FDG)
    • Brain-Amyloid Load measured by Positron Emission Tomography ([11C]-
    PIB)
    • CSF sAPP, Aß1-40, Aß1-42; total Tau, phospho-Tau
    • Blood sAPP
    E.2.2Secondary objectives of the trial
    Secondary:
    Placebo-controlled comparison of the efficacy of PT,
    15 mg BID based on the following parameters:

    • Cognitive Performance: ADAS-cog+
    • Episodic memory: Kungsholmen Word Recall and Word Recognition Test
    • Visual spatial ability : Clock Test-perception and drawing
    • Attention: Digit Symbol Substitution Test, Trail Making Test A and B
    • Measurement of Phenserine concentrations in CSF and plasma
    • Measurement of Acetylcholinesterase and Butyryl-cholinesterase in
    plasma, red blood cells and CSF
    Placebo/active drug-controlled comparison of the safety of PT, 15 mg BID
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    Inclusion criteria
    • Signed informed consent by patient or the legally accepted representative
    prior to the initiation of any study specific procedures
    • Male or female patients of at least 50 years of age
    • Probable Alzheimer’s Disease consistent with NINCDS-ADRDA criteria
    • MRI or CT scan within the last 12 months prior to baseline shoud exclude
    other aetiologies than AD to the patients dementia symptoms (e.g
    stroke).
    • Mini-Mental state examination score (MMSE) between 20 and 26 inclusive
    • Modified Hachinsky ischemic score equal or below 4
    • Female patients must be at least 2 years post-menopausal or surgically
    sterile
    • Caregiver available, if not living in the same household, caregiver sees
    patient at least 4 times a week
    • Patients living at home, old people’s home or an institutional setting
    without continuous nursing care
    • General health status acceptable for a participation in a 6 month clinical
    trial
    • Subjects to be selected for participating in the study must undergo PET
    studies with [18F]-fluorodeoxy-glucose (FDG) as a part of the screening
    and show changes in cerebral metabolism consistent with AD
    E.4Principal exclusion criteria
    Exclusion criteria
    General
    • Violation of inclusion criteria not approved by clinical study director or
    study safety officer
    • Failure to perform or to evaluate screening or baseline examinations
    • Hospitalisation (except for study purposes or due to social reasons, e.g.
    hospitalisation to unburden the caregiver) or change of concomitant
    medication 4 weeks prior to screening or during screening period
    • Participation in another therapeutic clinical trial 3 months before baseline
    • Inability to swallow tablets

    Medical
    • Unsubstituted vitamin B12 or folate deficiency
    • Serum electrolytes (sodium, potassium, magnesium) out of normal range
    • Unsubstituted hypothyroidism with TSH >6,00 μU/ml
    • Juvenile onset diabetes mellitus
    • Adult onset diabetes mellitus insufficiently controlled (HbA1c >8 %)
    • Renal insufficiency with serum creatinine >2 mg/dl
    • Severe hypotension requiring treatment with more than 2 drugs
    • Lab values seriously abnormal, and/or more than 2 lab values abnormal
    not approved by clinical study director or study safety officer
    • Hypersensitivity to cholinergic drugs
    • Serious drug allergies
    • Malignant tumours within the last 5 years

    Cardiovascular
    • Myocardial infarction or unstable angina within the last 6 months before
    screening
    • History of more than 1 myocardial infarction during the last 5 years
    • Cardiomyopathy
    • Myocarditis
    • Atrial fibrillation
    • Severe hypotension requiring treatment with more than 2 drugs
    • Severe hypertension requiring treatment with more than 2 drugs
    • Bradycardia (frequency of heart beat <50/min.)
    • Tachycardia (frequency of heart beat >90/min.)
    • Presence of AV block (type II / Mobitz II and type III)
    • Congenital long QT syndrome
    • Sinus node dysfunction
    • Prolonged QTcB-interval (males >450 and females >470 msec)
    • QTcB dispersion >100 msec
    • Presence of U wave

    Psychiatric
    • Episode of major depression in medical history*)
    • History or presence of schizophrenia
    • Chronic intoxication or chronic substance use disorder with
    pharmaceuticals, drugs, alcohol or industrial poisons
    *) A major depression has to be excluded by the investigator. This will be done by appropriate scales or methods, if considered necessary, and documented in source data.

    Neurological
    • Stroke within 6 months before screening or concomitant with onset of
    dementia
    • Tumours, subdural haematoma or other space occupying processes on
    CT/MRI
    • Head trauma with loss of consciousness within 1 year before or concurrent
    with onset of dementia
    • Onset of dementia within 1 year following cardiac arrest, surgery with
    general anaesthesia or resuscitation
    • Degenerative CNS disease, e.g. M. Huntington, Jacob-Creutzfeld Disease,
    Downs Syndrome
    • Wernickes Encephalopathy
    • Acute or chronic CNS infection including tertiary syphilis

    Previous Medication
    • Acetylcholinesterase inhibitors 3 months before baseline
    • Any experimental drug 3 months before enrolment
    • Nootropics 1 month before screening
    • Promethazine, thioridazine, chlorprothixene, flunitrazepam or nitrazepam if
    not discontinued 2 weeks before screening
    • Antipsychotics if not given for sleep disturbances
    • Antidepressants, except stable treatment with SSRI´s for at least 3
    months prior to screening

    Concomitant Medication
    • Peripherally acting drugs with effects on cholinergic transmission
    • Immunosuppresants
    • Antiparkinsonian therapy
    • Antiepileptics
    • Centrally active anti-hypertensive drugs like clonidine, alpha methyl dopa,
    guanidine, guanfacine or moxonidine
    • Non-steroidal anti-inflammatory drugs 72 h before blood plasma or CSF
    sampling
    • Cholesterol lowering drugs inhibiting HMG CoA reductase (simvastatin,
    pravastatin, fluvastatin, atorvastatin, cerivastatin)
    • Chronic intake of opioid containing analgesics
    • Sedating H1 antihistamines
    • Systemic cortico-steroids

    PET Imaging
    • PET contraindications (severe, unstable diabetes)

    CSF sampling
    • Thrombocytopenia with platelet count <140*103/μl
    • Coagulation disorders
    • Local skin or soft tissue infection along the needle tract
    • Papilledema during funduscopy
    • Evidence of high CSF pressure in CT/MRI
    • Treatment with anticoagulantia
    E.5 End points
    E.5.1Primary end point(s)
    Primary:
    Placebo-controlled comparison of the efficacy of Phenserine-tartrate (PT,15 mg BID) based on the following end-points:

    • Cerebral Glucose metabolism using Positron Emission Tomography (FDG)
    • Brain-Amyloid Load measured by Positron Emission Tomography ([11C]-
    PIB)
    • CSF sAPP, Aß1-40, Aß1-42; total Tau, phospho-Tau
    • Blood sAPP
    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 Yes
    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) 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 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.8.1.7.1Other trial design description
    3 months double blind followed by 3 months open label
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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 Information not present in EudraCT
    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
    end of the trial = visit 6, or participation on extension study (please see protocol).

    Sponsor´s termination of the study:
    AXONYX reserves the right to discontinue the clinical study at any time for medical or administrative reasons. When feasible, a 30-day written notification will be tendered
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months12
    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 No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    demented patients, therefore caregiver have to consent as well.
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    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)
    there is a 26 week open label extension study offered to the enrolled patient.
    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 Decision2004-10-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2004-11-03
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2006-11-08
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    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.

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