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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01626378




Registration number
NCT01626378
Ethics application status
Date submitted
20/06/2012
Date registered
22/06/2012
Date last updated
14/03/2018

Titles & IDs
Public title
Safety and Efficacy Study Evaluating TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)
Scientific 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)
Secondary ID [1] 0 0
TRx-237-007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Behavioral Variant Frontotemporal Dementia (bvFTD) 0 0
Condition category
Condition code
Neurological 0 0 0 0
Dementias
Neurological 0 0 0 0
Alzheimer's disease
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders
Neurological 0 0 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TRx0237
Treatment: Drugs - Placebo

Experimental: TRx0237 200 mg/day group -

Placebo comparator: Placebo -


Treatment: Drugs: TRx0237
TRx0237 100 mg tablet will be administered twice daily.

Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R)
Timepoint [1] 0 0
52 weeks
Primary outcome [2] 0 0
Change from Baseline on Functional Activities Questionnaire (FAQ)
Timepoint [2] 0 0
52 weeks
Primary outcome [3] 0 0
Change from Baseline on whole brain volume (assessed by brain MRI)
Timepoint [3] 0 0
52 weeks
Secondary outcome [1] 0 0
Change from Baseline on Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III)
Timepoint [1] 0 0
52 weeks
Secondary outcome [2] 0 0
Change from Baseline on Frontotemporal Dementia Rating Scale (FRS)
Timepoint [2] 0 0
52 weeks
Secondary outcome [3] 0 0
Change from Baseline on Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC)
Timepoint [3] 0 0
52 weeks
Secondary outcome [4] 0 0
Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes
Timepoint [4] 0 0
52 weeks

Eligibility
Key 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
Minimum age
No limit
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2016
Sample size
Target
Accrual to date
Final
220
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Neuroscience Research Australia - Randwick
Recruitment hospital [2] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 0 0
Neurodegenerative Disorders Research Pty Ltd - West Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
6005 - West Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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Indiana
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Maryland
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Massachusetts
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Minnesota
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New Jersey
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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Utah
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Vermont
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Virginia
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Nova Scotia
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
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Canada
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Quebec
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Croatia
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Zagreb
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Germany
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Berlin
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Germany
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Hamburg
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Germany
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München
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Germany
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Ulm
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Italy
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Brescia
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Italy
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Chieti Scalo
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Italy
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Milano
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Italy
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Torino
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Netherlands
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Amsterdam
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Netherlands
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Den Bosch
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Netherlands
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Rotterdam
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Poland
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Poznan
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Poland
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Szczecin
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Romania
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Bucharest
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Singapore
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Singapore
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Spain
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Barcelona
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Spain
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Ceuta
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Spain
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Zaragoza
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Aberdeen
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Birmingham
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Cheltenham
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Derby
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Epping
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London
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Oxford
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Shrewsbury
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United Kingdom
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Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
TauRx Therapeutics Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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).
Trial website
https://clinicaltrials.gov/study/NCT01626378
Trial related presentations / publications
Pletnikova O, Sloane KL, Renton AE, Traynor BJ, Crain BJ, Reid T, Zu T, Ranum LP, Troncoso JC, Rabins PV, Onyike CU. Hippocampal sclerosis dementia with the C9ORF72 hexanucleotide repeat expansion. Neurobiol Aging. 2014 Oct;35(10):2419.e17-21. doi: 10.1016/j.neurobiolaging.2014.04.009. Epub 2014 Apr 18.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01626378