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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier:
NCT01689246
First received: September 14, 2012
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by TauRx Therapeutics Ltd:

Primary Outcome Measures:
  • Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [ Time Frame: 65 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Mini-Mental Status Examination (MMSE) [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Change in expected decline of whole brain volume as measured by brain MRI [ Time Frame: 39 weeks and 65 weeks ] [ Designated as safety issue: No ]
  • Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 833
Study Start Date: February 2013
Estimated Study Completion Date: February 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   up to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 associated with methemoglobinemia
  • Current or prior participation in a clinical trial as follows:

    • Clinical trial of a product for cognition within 3 months (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01689246

  Hide Study Locations
Locations
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
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
MD Clinical
Hallandale Beach, Florida, United States, 33009
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
Neurocare Center for Research
Newton, Massachusetts, United States, 02459
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 Atlantic Neuroscience Institute
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
SPRI
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
Bulgaria
UMHAT "Alexandrovska" Clinic of Psychiatry First Department of Psychiatry
Sofia, Bulgaria, 1431
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
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
Canada, Quebec
Douglas Mental Health University Institute
Montreal, Quebec, Canada, H4H 1R3
Croatia
University Hospital Centre Zagreb
Zagreb, Croatia, 10000
University Psychiatric Hospital Vrapce
Zagreb, Croatia, 10090
Germany
Neurozentrum Achim Dr. med. Andreas Mahler
Achim, Germany, 28832
Department of Psychiatry, Charité
Berlin, Germany, 14050
Charité, University Medicine Berlin, CBF, Neurology
Berlin, Germany, 12200
Italy
Istituto Neurologico Carlo Besta
Milano, Italy, 20133
Neurologia Ospedale Maggiore Policlinico
Milano, Italy, 20122
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
Gachon University Gil Medical Center
Incheon, Korea, Republic of
Inha University Hospital
Incheon, Korea, Republic of
Seoul National University Bundang Hospital
Seongnam-si, Korea, Republic of
Seoul St. Mary's Hospital
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Seoul National University Boramae Medical Center
Seoul, Korea, Republic of
Inje University Sanggye Paik Hospital
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Konkuk University Medical Center
Seoul, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Malaysia
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
Hospital Seberang Jaya
Pulau Pinang, Malaysia, 13700
Taiping Hospital
Taiping, Malaysia, 34000
Poland
Podlaskie Centrum Psychogeriatrii
Białystok, Poland, 15-732
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, 70-215
Usługi Lekarskie Sp.c Palasik, Żabierek
Warszawa, Poland, 00-669
MTZ Clinical Research Sp. z o.o.
Warszawa, Poland, 02-106
mMED
Warszawa, Poland, 01-697
Romania
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
Clinical Hospital of Psychiatry "Prof. Dr. Alexandru Obregia", Psychiatry Department XIII
Bucharest, Romania, 041915
Psychomedical Consult
Bucharest, Romania, 024072
Clinical Municipal Hospital "Dr. Gavril Curteanu", Psychiatry Department
Oradea, Romania, 410154
Psychiatry Hospital "Dr. Gheorghe Preda", Department of Psychiatry III
Sibiu, Romania, 550082
Psychiatry Hospital "Dr. Gheorghe Preda", Center of Mental Health
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
Mental Health Research Center of the Russian Academy of Medical Sciences
Moscow, Russian Federation, 115522
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
CityClinical Hospital #34, City Scientific Practical Neurological Center
Novosibirsk, Russian Federation, 630054
Saint Petersburg Psychoneurological Research Institute n. a. V.M. Bekhterev
Saint Petersburg, Russian Federation, 192019
Saint Nicholas Psychiatric Hospital
Saint Petersburg, Russian Federation, 190121
City Geriatric Medical and Social Center
Saint Petersburg, Russian Federation, 190103
Singapore
National neuroscience Institute (NNI)
Singapore, Singapore, 308433
National University Hospital (NUH)
Singapore, Singapore, 119223
Tan Tock Seng Hospital (TTSH)
Singapore, Singapore, 308433
Changi General Hospital
Singapore, Singapore, 529889
Spain
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
Taiwan
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
Charing Cross Hospital
London, United Kingdom, W6 8RF
Dementia Research Centre
London, United Kingdom, WC1N 3BG
Re: Cognition Health Ltd.
London, United Kingdom, W1G 9JF
MAC Clinical Research Ltd
Manchester, United Kingdom, M32 0UT
Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
TauRx Therapeutics Ltd
  More Information

Additional Information:
No publications provided

Responsible Party: TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier: NCT01689246     History of Changes
Other Study ID Numbers: TRx-237-015
Study First Received: September 14, 2012
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Malaysia: Ministry of Health
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan : Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by TauRx Therapeutics Ltd:
Alzheimer's Disease
Alzheimer Disease
TRx0237
AD
Neurodegenerative Diseases
Dementia
Brain Diseases

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 28, 2014