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    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   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:2011-005292-17
    Sponsor's Protocol Code Number:TRx-237-008
    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:2012-06-26
    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 number2011-005292-17
    A.3Full title of the trial
    A Double-Blind, Placebo-Controlled, Randomised, 4-Week Safety and Tolerability Study
    of LMTM in Subjects with Mild to Moderate Alzheimer’s Disease on Pre-Existing Stable
    Acetylcholinesterase Inhibitor and/or Memantine Therapy
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A comparison study of LMTM and placebo in patients with Alzheimer’s Disease currently taking pre-specified medications
    A.3.2Name or abbreviated title of the trial where available
    TRx-237-008
    A.4.1Sponsor's protocol code numberTRx-237-008
    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 SponsorTauRx Therapeutics Ltd
    B.1.3.4CountrySingapore
    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 supportTauRx Therapeutics Ltd
    B.4.2CountrySingapore
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTauRx Therapeutics Ltd
    B.5.2Functional name of contact pointInformation Desk
    B.5.3 Address:
    B.5.3.1Street AddressLiberty Building, University of Aberdeen, Foresterhill Road
    B.5.3.2Town/ cityAberdeen
    B.5.3.3Post codeAB25 2ZP
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+441224 555191
    B.5.5Fax number+441224 555173
    B.5.6E-mailinfo@taurx.com
    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 nameLeuco-methylthioninium bis(hydromethanesulfonate)
    D.3.2Product code TRx0237
    D.3.4Pharmaceutical form Tablet
    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 INNMethylthioninium
    D.3.9.1CAS number 1236208-20-0
    D.3.9.2Current sponsor codeTRx0237
    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 number125
    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 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
    E.1.1.1Medical condition in easily understood language
    Alzheimer’s Disease
    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 14.1
    E.1.2Level LLT
    E.1.2Classification code 10001896
    E.1.2Term Alzheimer's disease
    E.1.2System Organ Class 100000004852
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the safety and tolerability of leuco-methylthioninium bis(hydromethanesulfonate) (LMTM) 250 mg daily when co-administered with an acetylcholinesterase inhibitor (AChEI) and/or memantine to patients with mild to moderate Alzheimer’s disease. As exploratory objectives, markers of monoamine oxidase (MAO) inhibition will be assessed and blood samples collected for separate population pharmacokinetic analysis.
    E.2.2Secondary objectives of the trial
    N/A
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Diagnosis according to NIA/AA criteria of
    • All cause dementia and
    • Probable Alzheimer’s disease
    2. MMSE score of 14-26 (inclusive) at Screening
    3. Cognitive impairment present for at least 6 months
    4. Age ≤ 90 years
    5. Modified Hachinski ischemic score of ≤ 4 at Screening
    6. Females must meet one of the following:
    • Surgically sterile (hysterectomy, bilateral salpingectomy / oophorectomy) for at least 6 months minimum
    • Have undergone bilateral tubal /occlusion / ligation at least 6 months prior
    • Post-menopausal for at least 1 year (confirmed by follicle stimulating hormone [FSH] level at Screening ≥ 30 mIU/mL; if a female patient is on hormone replacement therapy [HRT], a decision regarding FSH levels will be made by the investigator on a case by case basis)
    • Using adequate contraception (such as condoms, diaphragm or cervical/vault caps with spermicidal foam, gel, film, cream, suppository; intrauterine device or system, oral or long acting injected or implanted hormonal contraceptives for at least 3 months prior to Baseline; or vasectomised partner [with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate]); or true abstinence (when this is in line with the preferred and usual lifestyle of the patient; periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception); patients must agree to continue to maintain adequate contraception throughout participation in the study (until the final off-treatment visit).
    7. Patient is able to read, understand, and provide written informed consent in the designated language of the study site
    8. Has one or more identified caregivers who are able to verify daily compliance with study drug and provide information on safety and tolerability. The caregiver(s) must also give consent to participate.
    9. Currently taking an AChEI (i.e., donepezil, galantamine, or rivastigmine) and/or memantine:
    • The patient must have been taking such medication(s) for ≥ 3 months
    • The current dosage regimen and dosage form must be within the locally approved dose range and must have remained stable for ≥ 6 weeks before Baseline (Visit 2)
    • It must be planned that the dosage regimen will remain stable throughout participation in the study
    10. Able to comply with the study procedures in the view of the investigator
    E.4Principal exclusion criteria
    1. Significant CNS disorder other than Alzheimer’s disease (e.g., Parkinson’s disease, multiple sclerosis, progressive supranuclear palsy, hydrocephalus, Huntington’s disease)
    2. Patients in whom baseline MRI is contraindicated such as metal implants in head (except dental), pacemaker, and cochlear implants. MRI obtained using 1.5 or 3 Tesla machines using T1, T2*-weighted gradient-recalled echo and FLAIR sequences of sufficient quality at screening or within a maximum of 28 days before Baseline demonstrating:
    oSignificant intracranial pathology that would lead to a diagnosis other than probable Alzheimer’s disease
    o>4 cerebral microhaemorrhages (regardless of their anatomical location or diagnostic characterisation as “possible” or “definite”), any single area of superficial siderosis, or evidence of a prior macrohaemorrhage
    3. Clinical evidence or history of any of the following within specified period:
    •Cerebrovascular accident (2 years)
    •Transient ischemic attack (6 months)
    •Significant head injury with associated loss of consciousness, skull fracture or persisting cognitive impairment (2 years)
    •Other unexplained or recurrent loss of consciousness (2 years)
    4. Epilepsy (a single prior seizure related to the patient’s Alzheimer’s disease or seizures limited to childhood febrile seizures is considered acceptable)
    5. DSM-IV-TR criteria met for current major depressive disorder or schizophrenia or other psychotic disorders, bipolar disorder (within the past 5 years), or substance (including alcohol) related disorders (within the past 2 years)
    6. Resides in a hospital or continuous care facility
    7. History of swallowing difficulties
    8. Pregnant or breastfeeding
    9. History of significant haematological abnormality or current acute or chronic clinically significant abnormality, including:
    •History of hereditary or acquired methaemoglobinaemia or baseline measurement of MetHb >2.0% (confirmed on repeat)
    •History of haemoglobinopathy, myelodysplastic syndrome, haemolytic anaemia, or splenectomy
    •G6PD
    •Baseline value below age/sex appropriate lower limit of the central laboratory normal range for haemoglobin
    10. Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator. In addition, patients with the following abnormalities must be excluded:
    •Creatinine clearance <30 mL/min at Screening
    •TSH above laboratory normal range
    11. Clinically significant cardiovascular disease or abnormal assessments at Screening or Baseline, such as:
    •Hospitalisation for acute coronary syndrome (acute myocardial infarction or unstable angina) or symptoms consistent with angina pectoris, within the preceding 12 months
    •Signs or symptoms of clinical heart failure within the preceding 12 months
    •Evidence of atrial fibrillation on Screening ECG or history of atrial fibrillation that is not currently controlled
    •QTcB >450 msec in males or >470 msec in females, or low or flat T waves making measurement of QT interval unreliable
    •Recent history of poorly controlled hypertension, systolic blood pressure >160 mmHg, or diastolic blood pressure >100 mmHg
    •Systolic blood pressure <100 mmHg
    •Heart rate <48 bpm or >96 bpm
    •Significant orthostatic hypotension (decrease in systolic blood pressure of >20 mmHg after 2 minutes upon standing from seated position)
    12. Pre-existing or current signs or symptoms of respiratory failure
    •Patients previously diagnosed with moderate to severe sleep apnoea not adequately controlled should be excluded
    13. Concurrent acute or chronic clinically significant immunologic, renal, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than Alzheimer’s disease
    •Patients with primary biliary cirrhosis should be excluded
    •Diagnosis of cancer within the past 2 years (other than basal cell or squamous cell skin cancer or Stage 1 prostate cancer) unless treatment has resulted in complete freedom from disease for at least 2 years.
    14. Prior intolerance to MT-containing drug or any of the excipients
    15. Treatment currently or within 3 months before Baseline with any of the following medications (unless otherwise noted):
    •Tacrine
    •Anxiolytics and/or sedatives/hypnotics (exceptions: sedation for MRI or occasional short-acting benzodiazepines, chloral hydrate, or zolpidem as needed at bedtime)
    •Antipsychotics
    oClozapine, chlorpromazine, thioridazine, or ziprasidone
    oOther antipsychotics initiated within 3 months before Baseline or used in a regimen that has not been stable for at least 3 months
    •Carbamazepine
    •Drugs associated with methaemoglobinaemia (e.g., dapsone, local anesthetics such as benzocaine used chronically, primaquine and related antimalarials, sulfonamides)
    •Warfarin (and other Coumadin derivates such as phenprocouman)
    16. Current or prior participation in a clinical trial in which the last dose was received within 28 days prior to Baseline.
    E.5 End points
    E.5.1Primary end point(s)
    All adverse events (AEs), vital signs, 12-lead ECGs, clinical laboratory findings, physical and neurological examinations, and the potential for suicide or self-harm.
    E.5.1.1Timepoint(s) of evaluation of this end point
    • Adverse events will be recorded at Visits 1 to 7
    • Vital signs will be measured at Visits 1 to 7 for blood pressure and pulse and at Visits 2 to 7 for oral temperature and respiratory rate
    •12-lead ECG will be recorded at Visits 1 to 7
    •Clinical laboratory tests will be performed at Visits 1, 2, 4, 5, 6, and 7
    •Physical and neurological examinations will take place at Visits 1 to 7
    •Serotonin toxicity assessments will be performed at Visits 2 to 7
    •The potential for suicide or self-harm (Columbia Suicide Severity Rating Scale) will be assessed at Visits 2 to 7
    •Methaemoglobin will be measured at Visits 1 to 7
    E.5.2Secondary end point(s)
    N/A
    E.5.2.1Timepoint(s) of evaluation of this end point
    N/A
    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 No
    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 Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    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 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.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA13
    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
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    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: 20
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 No
    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
    For those patients who are receiving serotonergic medication, the identified caregiver(s) also must provide written consent to his/her own participation as outlined above. The caregiver will also be given a caregiver information sheet.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 60
    F.4.2.2In the whole clinical trial 60
    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)
    Expected standard treatment for the condition.
    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 Decision2012-06-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-07-31
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2013-03-11
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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
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