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

Phase 3

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: TRx0237 250 mg/day
Drug: TRx0237 150 mg/day
Drug: Placebo

Registration Number: NCT01689246

Lead Sponsor: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 891

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TRx0237 250 mg/day	TRx0237 250 mg/day	-
TRx0237 150 mg/day	TRx0237 150 mg/day	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)	65 weeks
Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)	65 weeks
Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes	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

Name	Time	Method
Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)	65 weeks
Change from Baseline on Mini-Mental Status Examination (MMSE)	65 weeks
Change in expected decline of whole brain volume as measured by brain MRI	39 weeks and 65 weeks

Trial Locations

Locations (117): Brain Matters Research
🇺🇸
Delray Beach, Florida, United States
NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
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Katowice, Poland
Gabinet Neurologiczny, Indywidualna Specjalistyczna Praktyka Lekarska
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Mosina, Poland
NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Lekarzy
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Poznań, Poland
Euromedis Sp. z o.o.
🇵🇱
Szczecin, Poland
Usługi Lekarskie Sp.c Palasik, Żabierek
🇵🇱
Warszawa, Poland
Mental Health Research Center of the Russian Academy of Medical Sciences, Gerontopsychiatry department
🇷🇺
Moscow, Russian Federation
University Psychiatric Hospital Vrapce
🇭🇷
Zagreb, Croatia
University Malaya Medical Centre
🇲🇾
Kuala Lumpur, Malaysia
MTZ Clinical Research Sp. z o.o.
🇵🇱
Warszawa, Poland
Psychiatry Hospital "Dr. Gheorghe Preda", Department of Psychiatry III
🇷🇴
Sibiu, Romania
National Neuroscience Institute (NNI)
🇸🇬
Singapore, Singapore
Changhua Christian Hospital
🇨🇳
Changhua, Taiwan
Medical and Cognitive Research Unit, Austin Health Heidelberg Repatriation Hospital
🇦🇺
Heidelberg West, Victoria, Australia
Non-governmental Healthcare Institution "Central Clinical Hospital #6 of the JSC "Russian Railways"
🇷🇺
Moscow, Russian Federation
UMHAT "Alexandrovska" Clinic of Neurology Diseases Department of Neurodegenerative and Immune and Infectious Diseases of Central Nervous System with Sector for Treatment of Neuroinfections
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Sofia, Bulgaria
Podlaskie Centrum Psychogeriatrii
🇵🇱
Białystok, Poland
State Budgetary Healthcare Institution of Sverdlovsk region "Sverdlovsk Regional Clinical Psychiatric Hospital"
🇷🇺
Ekaterinburg, Russian Federation
Saint Petersburg Psychoneurological Research Institute n. a. V.M. Bekhterev
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Saint Petersburg, Russian Federation
Advanced Memory Research Institute of NJ PC
🇺🇸
Toms River, New Jersey, United States
Okanagan Clinical Trials
🇨🇦
Kelowna, British Columbia, Canada
En Chu Kong Hospital
🇨🇳
Taipei, Taiwan
National Yang-Ming University School of Medicine
🇨🇳
Taipei, Taiwan
University Emergency Central Military Hospital "Dr.Carol Davila", Psychiatry Department
🇷🇴
Bucharest, Romania
CityClinical Hospital #34, City Scientific Practical Neurological Center
🇷🇺
Novosibirsk, Russian Federation
University Kuala Lumpur Royal College of Medicine
🇲🇾
Ipoh, Malaysia
Tan Tock Seng Hospital (TTSH)
🇸🇬
Singapore, Singapore
Changi General Hospital
🇸🇬
Singapore, Singapore
Pacific Research Network
🇺🇸
San Diego, California, United States
Xenoscience, Inc/ 21st Century Neurology
🇺🇸
Phoenix, Arizona, United States
San Francisco Clinical Research Center
🇺🇸
San Francisco, California, United States
Neurologia Ospedale Maggiore Policlinico
🇮🇹
Milano, Italy
IRCCS Istituto neurologico Casimiro Mondino
🇮🇹
Pavia, Italy
Clinica Neurologica, Università di Perugia-Ospedale S. Maria della Misericordia
🇮🇹
Perugia, Italy
Azienda Ospedaliera S.maria Della Misericordia
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Udine, Italy
U.O. Di Neurologia Ospedale di Circolo e Fondazione Macchi
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Varese, Italy
Azienda Ospedaliera Universitaria Sant'Andrea di Roma- Unita' di Neurologia
🇮🇹
Roma, Italy
University Hospital Centre Zagreb
🇭🇷
Zagreb, Croatia
FutureSearch Trials of Neurology
🇺🇸
Austin, Texas, United States
Istituto Neurologico Carlo Besta
🇮🇹
Milano, Italy
Dipartimento di Neuroscienze Universita' di Torino
🇮🇹
Torino, Italy
ActivMed Practices & Research
🇺🇸
Methuen, Massachusetts, United States
Memory Enhancement Centers of America, Inc
🇺🇸
Eatontown, New Jersey, United States
SPRI
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Brooklyn, New York, United States
CNS Healthcare, Inc
🇺🇸
Jacksonville, Florida, United States
Compass Research, LLC-North Clinic
🇺🇸
Leesburg, Florida, United States
Discipline of Psychiatry, University of Qld
🇦🇺
Herston, Queensland, Australia
McCusker Alzheimer's Research Foundation Inc
🇦🇺
Nedlands, Western Australia, Australia
Toronto Memory Program
🇨🇦
North York, Ontario, Canada
CRI Worldwide
🇺🇸
Marlton, New Jersey, United States
Neurological Associates of Albany, P. C.
🇺🇸
Albany, New York, United States
Inha University Hospital
🇰🇷
Incheon, Korea, Republic of
Olive Branch Family Medical
🇺🇸
Olive Branch, Mississippi, United States
The Cognitive Research Center of New Jersey
🇺🇸
Springfield, New Jersey, United States
UMHAT "Alexandrovska" Clinic of Psychiatry First Department of Psychiatry
🇧🇬
Sofia, Bulgaria
Neurodegenerative Disorders Research Pty Ltd
🇦🇺
Perth, Western Australia, Australia
Royal Adelaide Hospital Memory Trials Centre
🇦🇺
Adelaide, South Australia, Australia
Alexian Brothers Neurosciences Institute
🇺🇸
Elk Grove, Illinois, United States
True North Clinical Research Kentville Inc
🇨🇦
Kentville, Nova Scotia, Canada
Taiping Hospital
🇲🇾
Taiping, Malaysia
Hospital Sultan Ismail
🇲🇾
Johor Bahru, Malaysia
Hospital Universitario de Ceuta
🇪🇸
Ceuta, Spain
Seoul National University Bundang Hospital
🇰🇷
Seongnam-si, Korea, Republic of
Hospital Reina Sofía
🇪🇸
Córdoba, Spain
Konkuk University Medical Center
🇰🇷
Seoul, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷
Incheon, Korea, Republic of
Pallmed sp zoo prowadząca NZOZ Dom Sue Ryder; Centrum Psychoneurologii Wieku Podeszłego
🇵🇱
Bydgoszcz, Poland
Samsung Medical Center
🇰🇷
Seoul, Korea, Republic of
CMDTA "Neomed"
🇷🇴
Brasov, Romania
Psychomedical Consult
🇷🇴
Bucharest, Romania
County Emergency Clinical Hospital Arad, Psychiatry Department
🇷🇴
Arad, Romania
Hospital Viamed Montecanal
🇪🇸
Zaragoza, Spain
Clinical Municipal Hospital "Dr. Gavril Curteanu", Psychiatry Department
🇷🇴
Oradea, Romania
City Geriatric Medical and Social Center
🇷🇺
Saint Petersburg, Russian Federation
Psychiatry Hospital "Dr. Gheorghe Preda", Center of Mental Health
🇷🇴
Sibiu, Romania
Emergency Clinical County Hospital Sibiu, Neurology Department
🇷🇴
Sibiu, Romania
Hospital Clinico San Carlos
🇪🇸
Madrid, Spain
Chang Gung Memorial Hospital, Kaohsiung
🇨🇳
Kaohsiung, Taiwan
MAC Clinical Research Ltd
🇬🇧
Manchester, United Kingdom
Southampton General Hospital
🇬🇧
Southampton, United Kingdom
Dong-A Medical Center
🇰🇷
Busan, Korea, Republic of
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Inje University Sanggye Paik Hospital
🇰🇷
Seoul, Korea, Republic of
Neurozentrum Achim Dr. med. Andreas Mahler
🇩🇪
Achim, Germany
Memory Clinic, ECRC
🇩🇪
Berlin, Germany
Memory Unit, Neurology, The Queen Elizabeth Hospital
🇦🇺
Woodville South, South Australia, Australia
Southern Neurology Pty Limited
🇦🇺
Kogarah, New South Wales, Australia
Academic Department for Old Age Psychiatry, Prince of Wales Hospital
🇦🇺
Randwick, New South Wales, Australia
University of Southern California
🇺🇸
Los Angeles, California, United States
Miami Research Associates
🇺🇸
Miami, Florida, United States
Charité, University Medicine Berlin, CBF, Neurology
🇩🇪
Berlin, Germany
Seoul National University Boramae Medical Center
🇰🇷
Seoul, Korea, Republic of
Feldman, Robert MD
🇺🇸
Laguna Hills, California, United States
Shankle Clinic and Hoag Memorial Hospital Presbyterian
🇺🇸
Newport Beach, California, United States
JEM Research
🇺🇸
Atlantis, Florida, United States
iResearch Atlanta
🇺🇸
Decatur, Georgia, United States
Neurobehavioral Clinical Research
🇺🇸
Canton, Ohio, United States
The Clinical Trial Center, LLC
🇺🇸
Jenkintown, Pennsylvania, United States
Division of Rehabilitation and Aged Care
🇦🇺
Hornsby, New South Wales, Australia
Universita' Cattolica del Sacro Cuore
🇮🇹
Roma, Italy
mMED
🇵🇱
Warszawa, Poland
Saint Nicholas Psychiatric Hospital
🇷🇺
Saint Petersburg, Russian Federation
Mental Health Research Center of the Russian Academy of Medical Sciences
🇷🇺
Moscow, Russian Federation
National University Hospital (NUH)
🇸🇬
Singapore, Singapore
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
China Medical University Hospital
🇨🇳
Taichung, Taiwan
Chang Gung Memorial Hospital, Linkou
🇨🇳
Taoyuan, Taiwan
NHS Grampian, Department of Old Age Psychiatry Royal Cornhill Hospital
🇬🇧
Aberdeen, United Kingdom
Belfast Health and Social Care Trust (BHSCT)
🇬🇧
Belfast, United Kingdom
Re: Cognition Health Ltd.
🇬🇧
London, United Kingdom
RICE - The Research Institute for the Care of Older People
🇬🇧
Bath, United Kingdom
The Barberry Centre
🇬🇧
Birmingham, United Kingdom
Dementia Research Centre
🇬🇧
London, United Kingdom
Yale University School of Medicine
🇺🇸
New Haven, Connecticut, United States
Compass Research, LLC
🇺🇸
Orlando, Florida, United States
Charing Cross Hospital
🇬🇧
London, United Kingdom