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Safety and Efficacy Study Evaluating TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)

This study has been completed.
Information provided by (Responsible Party):
TauRx Therapeutics Ltd Identifier:
First received: June 20, 2012
Last updated: April 7, 2016
Last verified: April 2016
The purpose of this study is to demonstrate the safety and efficacy of TRx0237 in the treatment of patients with behavioral variant frontotemporal dementia (bvFTD).

Condition Intervention Phase
Behavioral Variant Frontotemporal Dementia (bvFTD)
Drug: TRx0237
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: A Double-Blind, Placebo-Controlled, Randomized, Parallel Group, 12-Month Safety and Efficacy Trial of TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)

Resource links provided by NLM:

Further study details as provided by TauRx Therapeutics Ltd:

Primary Outcome Measures:
  • Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Functional Activities Questionnaire (FAQ) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on whole brain volume (assessed by brain MRI) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline on Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Frontotemporal Dementia Rating Scale (FRS) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    Safety parameters included adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, assessment of serotonin syndrome, brain magnetic resonance imaging (MRI) and potential for suicidal behavior and thoughts

Other Outcome Measures:
  • Early effect on modified ADCS-CGIC (change from Baseline) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on the rate of atrophy in frontal and temporal lobes as well as ventricular volume (assessed by brain MRI) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Mini-Mental Status Examination (MMSE) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Addenbrooke's Cognitive Examination-III (ACE-III) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TRx0237 in subjects with known genetic mutations associated with bvFTD [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 220
Study Start Date: May 2013
Study Completion Date: February 2016
Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TRx0237 200 mg/day group Drug: TRx0237
TRx0237 100 mg tablet will be administered twice daily.
Placebo Comparator: Placebo Drug: Placebo
Placebo tablets will be administered twice daily. The 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.


Ages Eligible for Study:   up to 79 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of probable bvFTD
  • Centrally rated frontotemporal atrophy score of 2 or greater on brain MRI
  • MMSE ≥20
  • Age <80 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, 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 bvFTD
  • Significant intracranial pathology seen on brain MRI scan
  • Biomarker evidence of underlying Alzheimer's disease pathology
  • Expressive language deficits
  • Meets research criteria for Amyotrophic Lateral Sclerosis or motor neuron disease
  • Meets diagnostic criteria for probable bvFTD but has a proven mutation producing non-tau, non-TDP-43 pathology
  • Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness ≥15 minutes
  • Epilepsy
  • Rapid eye movement sleep behavior disorder
  • Major depressive disorder, schizophrenia, or other psychotic disorders, bipolar disorder, 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 bvFTD
  • 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 90 days before Baseline with any of the following medications (unless otherwise noted):

    • Tacrine
    • Amphetamine or dexamphetamine
    • Clozapine, olanzapine (and there is no intent to initiate therapy during the course of the study)
    • Carbamazepine, primidone
    • Drugs for which there is 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, 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 identifier: NCT01626378

  Hide Study Locations
United States, California
David Geffen School of Medicine at UCLA, UCLA Neurological Services
Los Angeles, California, United States, 90095
The Shankle Clinic
Newport Beach, California, United States, 92663
Memory and Aging Centre
San Francisco, California, United States, 94158
United States, Florida
Meridien Research
Brooksville, Florida, United States, 34601
Mayo Clinic
Jacksonville, Florida, United States, 32224
Compass Research, LLC
Orlando, Florida, United States, 32806
University of South Florida
Tampa, Florida, United States, 33613
United States, Georgia
Department of Neurology, Emory University
Atlanta, Georgia, United States, 30329
United States, Illinois
Alexian Brothers Neurosciences Institute Clinical Research
Elk Grove Village, Illinois, United States, 60007
United States, Indiana
Indiana University Department of Neurology
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21224
United States, Massachusetts
Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
Mayo Clinic, Department of Neurology
Rochester, Minnesota, United States, 55905
United States, New Jersey
Memory Enhancement Center of America, Inc.
Eatontown, New Jersey, United States, 07724
United States, New York
Neurological Associates of Albany, P. C.
Albany, New York, United States, 12208
Integrative Clinical Trials LLC
Brooklyn, New York, United States, 11229
United States, North Carolina
UNC Department of Neurology, Physicians Office Building
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
University Hospitals Case Medical Center, Neurology Clinical Trials Unit
Cleveland, Ohio, United States, 44106
United States, Oklahoma
Rivers Wellness and Research Institute
Oklahoma City, Oklahoma, United States, 73112
United States, Pennsylvania
The Clinical Trial Center, LLC
Jenkintown, Pennsylvania, United States, 19046
Hospital of the University of Pennsylvania, Department of Neurology
Philadelphia, Pennsylvania, United States, 19104
United States, Utah
PRA Health Sciences, Phase 2/3 Outpatient and CNS Clinic
Salt Lake City, Utah, United States, 84106
United States, Vermont
The Memory Clinic
Bennington, Vermont, United States, 05201
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22903
Australia, New South Wales
Neuroscience Research Australia
Randwick, New South Wales, Australia, 2031
Australia, Victoria
Box Hill Hospital
Box Hill, Victoria, Australia, 3128
Australia, Western Australia
Neurodegenerative Disorders Research Pty Ltd
West Perth, Western Australia, Australia, 6005
Canada, Alberta
Heritage Medical Research Clinic-University of Calgary
Calgary, Alberta, Canada, T2N 4Z6
Canada, British Columbia
University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders
Vancouver, British Columbia, Canada, V6T 2B5
Vancouver Island Health Authority
Victoria, British Columbia, Canada, V8R 1J8
Canada, Nova Scotia
True North Clinical Research
Halifax, Nova Scotia, Canada, B3S 1M7
Canada, Ontario
Geriatric Clinical Trials Group, Parkwood Institute
London, Ontario, Canada, N6C 0A7
Toronto Memory Program
Toronto, Ontario, Canada, M3B 2S7
University Health Network, Toronto Western Hospital, Memory Clinic
Toronto, Ontario, Canada, M5T 2S8
Canada, Quebec
McGill Centre for Studies in Aging, Alzheimer Disease Research Unit
Verdun, Quebec, Canada, H4H 1R3
University Hospital Centre Zagreb
Zagreb, Croatia, 10000
University Psychiatric Hospital Vrapče
Zagreb, Croatia, 10090
Charité-Universitätsmedizin Berlin Klinik für Psychiatrie und Psychotherapie
Berlin, Germany, 10117
Memory Clinic, ECRC
Berlin, Germany, 13125
Universitätsklinikum Hamburg-Eppendorf Klinik für Psychiatrie und Psychotherapie
Hamburg, Germany, 20246
Klinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München
München, Germany, 81675
Universitäts - und Rehabilitationskliniken Ulm, Neurologie
Ulm, Germany, 89081
Unità di Neuroimmagine e Epidemiologia Alzheimer
Brescia, Italy, 25125
Fondazione Universita' Gabriele D'Annunzio di Chieti
Chieti Scalo, Italy, 66100
Fondazione IRCCS Istituto Neurologico "Carlo Besta"
Milano, Italy, 20133
Neurology I, Department of Neuroscience, University of Torino
Torino, Italy, 10126
Alzheimer Research Center Amsterdam
Amsterdam, Netherlands, 1081
Jeroen Bosch Ziekenhuis, afdeling geriatrie
Den Bosch, Netherlands, 5223
Erasmus University Medical Center
Rotterdam, Netherlands, 3015
NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska
Poznań, Poland, 61-853
Euromedis Sp. z o.o.
Szczecin, Poland, 70-111
Psychomedical Consult
Bucharest, Romania, 024072
National Neuroscience Institute Department of Neurology
Singapore, Singapore, 308433
Fundació ACE. Institut Català de Neurociències Aplicades
Barcelona, Spain, 08028
Ceuta University Hospital; Neurology
Ceuta, Spain, 51003
Hospital Viamed Montecanal, Neurology Department
Zaragoza, Spain, 50012
United Kingdom
NHS Grampian, OAP Directorate
Aberdeen, United Kingdom, AB25 2ZH
The Barberry Out-Patients Department
Birmingham, United Kingdom, B15 2FG
2gether NHS foundation trust
Cheltenham, United Kingdom, GL53 9DZ
Kingsway Hospital
Derby, United Kingdom, DE22 3LZ
St Margaret's Hospital Mental Health Unit
Epping, United Kingdom, CM16 6TN
Cognition Health Ltd.
London, United Kingdom, W1G 9JF
Imperial College Healthcare NHS Trust - Charing Cross Hospital
London, United Kingdom, W6 8RF
Dementia Research Center at Queens Square
London, United Kingdom, WC1N 3BG
Nuffield Department of Clinical Neurosciences
Oxford, United Kingdom, OX3 9DU
Redwoods Centre
Shrewsbury, United Kingdom, SY3 5DS
Wessex Neurological Centre, Southampton General Hospital
Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
TauRx Therapeutics Ltd
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: TauRx Therapeutics Ltd Identifier: NCT01626378     History of Changes
Other Study ID Numbers: TRx-237-007 
Study First Received: June 20, 2012
Last Updated: April 7, 2016
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Croatia: Agency for Medicinal Product and Medical Devices
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Singapore: Health Sciences Authority
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by TauRx Therapeutics Ltd:
Behavioral Variant Frontotemporal Dementia
Frontotemporal Dementia

Additional relevant MeSH terms:
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms processed this record on October 21, 2016