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Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01689246
Recruitment Status : Completed
First Posted : September 21, 2012
Last Update Posted : March 14, 2018
Information provided by (Responsible Party):
TauRx Therapeutics Ltd

Brief Summary:
The purpose of this study is to determine the safety and efficacy of TRx0237 in the treatment of subjects with mild to moderate Alzheimer's Disease.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: TRx0237 150 mg/day Drug: TRx0237 250 mg/day Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 891 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 15-Month Trial of TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease
Study Start Date : January 2013
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: TRx0237 250 mg/day Drug: TRx0237 250 mg/day
TRx0237 125 mg tablets will be administered twice daily.

Placebo Comparator: Placebo Drug: Placebo
Placebo tablets will be administered twice daily. The active placebo tablets include 4 mg of TRx0237 as a urinary and fecal colorant to maintain blinding; hence the placebo group will receive a total of 8 mg/day of TRx0237.

Experimental: TRx0237 150 mg/day Drug: TRx0237 150 mg/day
TRx0237 75 mg tablets will be administered twice daily.

Primary Outcome Measures :
  1. Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) [ Time Frame: 65 weeks ]
  2. Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) [ Time Frame: 65 weeks ]
  3. Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [ Time Frame: 65 weeks ]
    Safety parameters include adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, potential for suicide and self-harm, brain magnetic resonance imaging (MRI), and potential for serotonin toxicity

Secondary Outcome Measures :
  1. Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: 65 weeks ]
  2. Change from Baseline on Mini-Mental Status Examination (MMSE) [ Time Frame: 65 weeks ]
  3. Change in expected decline of whole brain volume as measured by brain MRI [ Time Frame: 39 weeks and 65 weeks ]

Other Outcome Measures:
  1. Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging [ Time Frame: 39 weeks and 65 weeks ]
  2. Change in expected increase in ventricular volume and decline in hippocampal volume as evaluated by MRI [ Time Frame: 39 weeks and 65 weeks ]
  3. Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite [ Time Frame: 65 weeks ]
  4. Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture [ Time Frame: 65 weeks ]
  5. Compare the influence of Apolipoprotein E genotype on the primary and selected secondary outcomes in subjects by or for whom legally acceptable consent is separately provided [ Time Frame: 65 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 89 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of all cause dementia and probable Alzheimer's disease
  • Clinical Dementia Rating (CDR) total score of 1 (mild) to 2 (moderate) and MMSE score of 14-26 (inclusive)
  • Age < 90 years
  • Modified Hachinski ischemic score of ≤ 4
  • Females, if of child-bearing potential, must practice true abstinence or be competent to use adequate contraception and agree to maintain this throughout the study
  • Subject, and/or, in the case of reduced decision-making capacity, legally acceptable representative(s) consistent with national law is/are able to read, understand, and provide written informed consent
  • Has one (or more) identified adult caregiver who is willing to provide written informed consent for his/her own participation; is able to read, understand, and speak the designated language at the study site; either lives with the subject or sees the subject for ≥2 hours/day ≥3 days/week; agrees to accompany the subject to each study visit; and is able to verify daily compliance with study drug
  • If currently taking an acetylcholinesterase inhibitor and/or memantine at the time of Screening, the subject must have been taking such medication(s) for ≥3 months. The dosage regimen must have remained stable for ≥6 weeks and it must be planned to remain stable throughout participation in the study.
  • Able to comply with the study procedures

Exclusion Criteria:

  • Significant central nervous system (CNS) disorder other than Alzheimer's disease
  • Significant focal or vascular intracranial pathology seen on brain MRI scan
  • Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness ≥15 minutes
  • Epilepsy
  • Major depressive disorder, schizophrenia, or other psychotic disorders, bipolar disorder, or substance (including alcohol) related disorders
  • Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MRI
  • Resides in hospital or moderate to high dependency continuous care facility
  • History of swallowing difficulties
  • Pregnant or breastfeeding
  • Glucose-6-phosphate dehydrogenase deficiency
  • History of significant hematological abnormality or current acute or chronic clinically significant abnormality
  • Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator
  • Clinically significant cardiovascular disease or abnormal assessments
  • Preexisting or current signs or symptoms of respiratory failure
  • Concurrent acute or chronic clinically significant immunologic, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than Alzheimer's disease
  • Diagnosis of cancer within the past 2 years prior to Baseline (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
  • Prior intolerance or hypersensitivity to methylthioninium-containing drug, similar organic dyes, or any of the excipients
  • Treatment currently or within 3 months before Baseline with any of the following medications:

    • Tacrine
    • Clozapine, olanzapine (and there is no intent to initiate therapy during the course of the study)
    • Carbamazepine, primidone
    • Drugs with a warning or precaution in the labeling about methemoglobinemia at approved doses
  • Current or prior participation in a clinical trial as follows:

    • Clinical trial of a product for cognition within 3 months of Screening (unless confirmed to have been randomized to placebo)
    • A clinical trial of a drug, biologic, therapeutic device, or medical food in which the last dose/administration was received within 28 days prior to Baseline

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01689246

  Hide Study Locations
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United States, Arizona
Xenoscience, Inc/ 21st Century Neurology
Phoenix, Arizona, United States, 85004
United States, California
Feldman, Robert MD
Laguna Hills, California, United States, 92653
University of Southern California
Los Angeles, California, United States, 90033
Shankle Clinic and Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States, 92658
Pacific Research Network
San Diego, California, United States, 92103
San Francisco Clinical Research Center
San Francisco, California, United States, 94118
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06510
United States, Florida
JEM Research
Atlantis, Florida, United States, 33462
Brain Matters Research
Delray Beach, Florida, United States, 33445
CNS Healthcare, Inc
Jacksonville, Florida, United States, 32256
Compass Research, LLC-North Clinic
Leesburg, Florida, United States, 34748
Miami Research Associates
Miami, Florida, United States, 33143
Compass Research, LLC
Orlando, Florida, United States, 32806
United States, Georgia
iResearch Atlanta
Decatur, Georgia, United States, 30030
United States, Illinois
Alexian Brothers Neurosciences Institute
Elk Grove, Illinois, United States, 60007
United States, Massachusetts
ActivMed Practices & Research
Methuen, Massachusetts, United States, 01844
United States, Mississippi
Olive Branch Family Medical
Olive Branch, Mississippi, United States, 38654
United States, New Jersey
Memory Enhancement Centers of America, Inc
Eatontown, New Jersey, United States, 07724
CRI Worldwide
Marlton, New Jersey, United States, 08053
The Cognitive Research Center of New Jersey
Springfield, New Jersey, United States, 07801
Advanced Memory Research Institute of NJ PC
Toms River, New Jersey, United States, 08757
United States, New York
Neurological Associates of Albany, P. C.
Albany, New York, United States, 12208
Brooklyn, New York, United States, 11235
United States, Ohio
Neurobehavioral Clinical Research
Canton, Ohio, United States, 44718
United States, Pennsylvania
The Clinical Trial Center, LLC
Jenkintown, Pennsylvania, United States, 19046
United States, Texas
FutureSearch Trials of Neurology
Austin, Texas, United States, 78731
Australia, New South Wales
Division of Rehabilitation and Aged Care
Hornsby, New South Wales, Australia, 2077
Southern Neurology Pty Limited
Kogarah, New South Wales, Australia, 2217
Academic Department for Old Age Psychiatry, Prince of Wales Hospital
Randwick, New South Wales, Australia, 2031
Australia, Queensland
Discipline of Psychiatry, University of Qld
Herston, Queensland, Australia, 4006
Australia, South Australia
Royal Adelaide Hospital Memory Trials Centre
Adelaide, South Australia, Australia, 5000
Memory Unit, Neurology, The Queen Elizabeth Hospital
Woodville South, South Australia, Australia, 5011
Australia, Victoria
Medical and Cognitive Research Unit, Austin Health Heidelberg Repatriation Hospital
Heidelberg West, Victoria, Australia, 3081
Australia, Western Australia
McCusker Alzheimer's Research Foundation Inc
Nedlands, Western Australia, Australia, 6009
Neurodegenerative Disorders Research Pty Ltd
Perth, Western Australia, Australia, 6005
UMHAT "Alexandrovska" Clinic of Neurology Diseases Department of Neurodegenerative and Immune and Infectious Diseases of Central Nervous System with Sector for Treatment of Neuroinfections
Sofia, Bulgaria, 1431
UMHAT "Alexandrovska" Clinic of Psychiatry First Department of Psychiatry
Sofia, Bulgaria, 1431
Canada, British Columbia
Okanagan Clinical Trials
Kelowna, British Columbia, Canada, V1Y 1Z9
Canada, Nova Scotia
True North Clinical Research Kentville Inc
Kentville, Nova Scotia, Canada, B4N 4K9
Canada, Ontario
Toronto Memory Program
North York, Ontario, Canada, M3B 2S7
University Hospital Centre Zagreb
Zagreb, Croatia, 10000
University Psychiatric Hospital Vrapce
Zagreb, Croatia, 10090
Neurozentrum Achim Dr. med. Andreas Mahler
Achim, Germany, 28832
Charité, University Medicine Berlin, CBF, Neurology
Berlin, Germany, 12200
Memory Clinic, ECRC
Berlin, Germany, 13125
Neurologia Ospedale Maggiore Policlinico
Milano, Italy, 20122
Istituto Neurologico Carlo Besta
Milano, Italy, 20133
IRCCS Istituto neurologico Casimiro Mondino
Pavia, Italy, 27100
Clinica Neurologica, Università di Perugia-Ospedale S. Maria della Misericordia
Perugia, Italy, 06156
Universita' Cattolica del Sacro Cuore
Roma, Italy, 00168
Azienda Ospedaliera Universitaria Sant'Andrea di Roma- Unita' di Neurologia
Roma, Italy, 00189
Dipartimento di Neuroscienze Universita' di Torino
Torino, Italy, 10126
Azienda Ospedaliera S.maria Della Misericordia
Udine, Italy, 33100
U.O. Di Neurologia Ospedale di Circolo e Fondazione Macchi
Varese, Italy, 21100
Korea, Republic of
Dong-A Medical Center
Busan, Korea, Republic of, 602-715
Inha University Hospital
Incheon, Korea, Republic of, 400-711
Gachon University Gil Medical Center
Incheon, Korea, Republic of, 405-760
Seoul National University Bundang Hospital
Seongnam-si, Korea, Republic of, 463-707
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Inje University Sanggye Paik Hospital
Seoul, Korea, Republic of, 139-707
Konkuk University Medical Center
Seoul, Korea, Republic of, 143-729
Seoul National University Boramae Medical Center
Seoul, Korea, Republic of, 156-707
University Kuala Lumpur Royal College of Medicine
Ipoh, Malaysia, 30450
Hospital Sultan Ismail
Johor Bahru, Malaysia, 81100
University Malaya Medical Centre
Kuala Lumpur, Malaysia, 50603
Taiping Hospital
Taiping, Malaysia, 34000
Podlaskie Centrum Psychogeriatrii
Białystok, Poland, 15-756
Pallmed sp zoo prowadząca NZOZ Dom Sue Ryder; Centrum Psychoneurologii Wieku Podeszłego
Bydgoszcz, Poland, 85-796
NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
Katowice, Poland, 40-123
Gabinet Neurologiczny, Indywidualna Specjalistyczna Praktyka Lekarska
Mosina, Poland, 62-050
NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Lekarzy
Poznań, Poland, 61-853
Euromedis Sp. z o.o.
Szczecin, Poland, 70-111
Usługi Lekarskie Sp.c Palasik, Żabierek
Warszawa, Poland, 00-669
Warszawa, Poland, 01-697
MTZ Clinical Research Sp. z o.o.
Warszawa, Poland, 02-106
County Emergency Clinical Hospital Arad, Psychiatry Department
Arad, Romania, 310022
CMDTA "Neomed"
Brasov, Romania, 500283
University Emergency Central Military Hospital "Dr.Carol Davila", Psychiatry Department
Bucharest, Romania, 010816
Psychomedical Consult
Bucharest, Romania, 024072
Clinical Municipal Hospital "Dr. Gavril Curteanu", Psychiatry Department
Oradea, Romania, 410154
Psychiatry Hospital "Dr. Gheorghe Preda", Center of Mental Health
Sibiu, Romania, 550082
Psychiatry Hospital "Dr. Gheorghe Preda", Department of Psychiatry III
Sibiu, Romania, 550082
Emergency Clinical County Hospital Sibiu, Neurology Department
Sibiu, Romania, 550166
Russian Federation
State Budgetary Healthcare Institution of Sverdlovsk region "Sverdlovsk Regional Clinical Psychiatric Hospital"
Ekaterinburg, Russian Federation, 620030
Non-governmental Healthcare Institution "Central Clinical Hospital #6 of the JSC "Russian Railways"
Moscow, Russian Federation, 109388
Mental Health Research Center of the Russian Academy of Medical Sciences, Gerontopsychiatry department
Moscow, Russian Federation, 115522
Mental Health Research Center of the Russian Academy of Medical Sciences
Moscow, Russian Federation, 115522
CityClinical Hospital #34, City Scientific Practical Neurological Center
Novosibirsk, Russian Federation, 630054
City Geriatric Medical and Social Center
Saint Petersburg, Russian Federation, 190103
Saint Nicholas Psychiatric Hospital
Saint Petersburg, Russian Federation, 190121
Saint Petersburg Psychoneurological Research Institute n. a. V.M. Bekhterev
Saint Petersburg, Russian Federation, 192019
National University Hospital (NUH)
Singapore, Singapore, 119223
National Neuroscience Institute (NNI)
Singapore, Singapore, 308433
Tan Tock Seng Hospital (TTSH)
Singapore, Singapore, 308433
Changi General Hospital
Singapore, Singapore, 529889
Hospital Universitario de Ceuta
Ceuta, Spain, 51003
Hospital Reina Sofía
Córdoba, Spain, 14011
Hospital Clinico San Carlos
Madrid, Spain, 28040
Hospital Viamed Montecanal
Zaragoza, Spain, 50006
Changhua Christian Hospital
Changhua, Taiwan
Chang Gung Memorial Hospital, Kaohsiung
Kaohsiung, Taiwan
China Medical University Hospital
Taichung, Taiwan
En Chu Kong Hospital
Taipei, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
National Yang-Ming University School of Medicine
Taipei, Taiwan
Chang Gung Memorial Hospital, Linkou
Taoyuan, Taiwan
United Kingdom
NHS Grampian, Department of Old Age Psychiatry Royal Cornhill Hospital
Aberdeen, United Kingdom, AB25 2ZH
RICE - The Research Institute for the Care of Older People
Bath, United Kingdom, BA1 3NG
Belfast Health and Social Care Trust (BHSCT)
Belfast, United Kingdom, BT12 6BA
The Barberry Centre
Birmingham, United Kingdom, B15 2SG
MAC Clinical Research Ltd
Blackpool, United Kingdom, FY2 0JH
MAC Clinical Research Ltd
Bradford, United Kingdom, BD3 0DQ
MAC Clinical Research Ltd
Cannock, United Kingdom, WS11 0BN
MAC Clinical Research Ltd
Leeds, United Kingdom, LS10 1DU
Re: Cognition Health Ltd.
London, United Kingdom, W1G 9JF
Charing Cross Hospital
London, United Kingdom, W6 8RF
Dementia Research Centre
London, United Kingdom, WC1N 3BG
MAC Clinical Research Ltd
Manchester, United Kingdom, M13 9NQ
Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
TauRx Therapeutics Ltd

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: TauRx Therapeutics Ltd Identifier: NCT01689246     History of Changes
Other Study ID Numbers: TRx-237-015
First Posted: September 21, 2012    Key Record Dates
Last Update Posted: March 14, 2018
Last Verified: March 2018
Keywords provided by TauRx Therapeutics Ltd:
Alzheimer's Disease
Alzheimer Disease
Neurodegenerative Diseases
Brain Diseases
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Methylene Blue
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action