Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.
 
ClinicalTrials.gov Identifier: NCT01626378
Recruitment Status : Completed
First Posted : June 22, 2012
Last Update Posted : March 14, 2018
Sponsor:
Information provided by (Responsible Party):
TauRx Therapeutics Ltd

Tracking Information
First Submitted Date  ICMJE June 20, 2012
First Posted Date  ICMJE June 22, 2012
Last Update Posted Date March 14, 2018
Study Start Date  ICMJE May 2013
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 7, 2016)
  • Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R) [ Time Frame: 52 weeks ]
  • Change from Baseline on Functional Activities Questionnaire (FAQ) [ Time Frame: 52 weeks ]
  • Change from Baseline on whole brain volume (assessed by brain MRI) [ Time Frame: 52 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2012)
  • Change from Baseline in Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: 52 weeks ]
  • Change from Baseline in Addenbrooke's Cognitive Examination - Revised (ACE-R) [ Time Frame: 52 weeks ]
Change History Complete list of historical versions of study NCT01626378 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 7, 2016)
  • Change from Baseline on Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III) [ Time Frame: 52 weeks ]
  • Change from Baseline on Frontotemporal Dementia Rating Scale (FRS) [ Time Frame: 52 weeks ]
  • Change from Baseline on Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC) [ Time Frame: 52 weeks ]
  • Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [ Time Frame: 52 weeks ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2012)
  • Change from Baseline in Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III) [ Time Frame: 52 weeks ]
  • Change from Baseline in Frontotemporal Dementia Rating Scale (FRS) [ Time Frame: 52 weeks ]
  • Change from Baseline in Functional Activities Questionnaire (FAQ) [ Time Frame: 52 weeks ]
Current Other Pre-specified Outcome Measures
 (submitted: April 7, 2016)
  • Early effect on modified ADCS-CGIC (change from Baseline) [ Time Frame: 8 weeks ]
  • 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 ]
  • Change from Baseline on Mini-Mental Status Examination (MMSE) [ Time Frame: 52 weeks ]
  • Change from Baseline on Addenbrooke's Cognitive Examination-III (ACE-III) [ Time Frame: 52 weeks ]
  • Determine the effect of TRx0237 in subjects with known genetic mutations associated with bvFTD [ Time Frame: 52 weeks ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study Evaluating TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)
Official Title  ICMJE A Double-Blind, Placebo-Controlled, Randomized, Parallel Group, 12-Month Safety and Efficacy Trial of TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Behavioral Variant Frontotemporal Dementia (bvFTD)
Intervention  ICMJE
  • Drug: TRx0237
    TRx0237 100 mg tablet will be administered twice daily.
  • 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.
Study Arms  ICMJE
  • Experimental: TRx0237 200 mg/day group
    Intervention: Drug: TRx0237
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 19, 2015)
220
Original Estimated Enrollment  ICMJE
 (submitted: June 20, 2012)
180
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 79 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Croatia,   Germany,   Italy,   Netherlands,   Poland,   Romania,   Singapore,   Spain,   United Kingdom,   United States
Removed Location Countries Argentina,   Bulgaria,   Finland
 
Administrative Information
NCT Number  ICMJE NCT01626378
Other Study ID Numbers  ICMJE TRx-237-007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party TauRx Therapeutics Ltd
Study Sponsor  ICMJE TauRx Therapeutics Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account TauRx Therapeutics Ltd
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP