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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by TauRx Therapeutics Ltd
Sponsor:
Information provided by (Responsible Party):
TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier:
NCT01626378
First received: June 20, 2012
Last updated: June 10, 2014
Last verified: June 2014
  Purpose

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 Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R) [ 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 Functional Activities Questionnaire (FAQ) [ 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 whole brain 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 ]

Estimated Enrollment: 180
Study Start Date: August 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: July 2015 (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.

  Eligibility

Ages Eligible for Study:   up to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 focal or vascular 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; magnetic resonance compatible prosthetics, clips, stents, or any other device proven to be compatible will be allowed
  • 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 3 months 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 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, 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: NCT01626378

Contacts
Contact: Karen Pozzie 1-888-570-3142 info@dementiastudy.net

  Show 75 Study Locations
Sponsors and Collaborators
TauRx Therapeutics Ltd
  More Information

Additional Information:
No publications provided

Responsible Party: TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier: NCT01626378     History of Changes
Other Study ID Numbers: TRx-237-007
Study First Received: June 20, 2012
Last Updated: June 10, 2014
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
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
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
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
bvFTD
Frontotemporal Dementia

Additional relevant MeSH terms:
Dementia
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on July 28, 2014