Clinical trial NCT01689233: Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild Alzheimer's Disease
Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 18-Month Safety and Efficacy Study of TRx0237 in Subjects With Mild Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Alzheimer Disease
TRx0237
AD
Neurodegenerative Diseases
Dementia
Brain Diseases
Lead sponsor: TauRx Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2012-09-21
Enrollment: 800
Sex: ALL
Maximum age (years): 89
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and efficacy of TRx0237 in the treatment of subjects with mild Alzheimer's Disease.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of all cause dementia and probable Alzheimer's disease
* Clinical Dementia Rating (CDR) total score of 0.5 or 1 (mild) and MMSE score of 20-26 (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, 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 (unless otherwise noted):

  * 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 of methemoglobinemia at approved doses
* Current or prior participation in a clinical trial as follows:

  * Clinical trial of a product for cognition in which the last dose was received within 90 days prior to 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

Primary outcomes:
measure: Change from Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)
timeFrame: 78 weeks
measure: Change from Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)
timeFrame: 78 weeks
measure: Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes
timeFrame: 78 weeks
Secondary outcomes:
measure: Change from Baseline in Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)
timeFrame: 78 weeks
measure: Change from Baseline in Mini-Mental Status Examination (MMSE)
timeFrame: 78 weeks
measure: Change from Baseline in Neuropsychiatric Inventory (NPI)
timeFrame: 78 weeks
measure: Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: 78 weeks
measure: Change in expected decline of whole brain volume as measured by brain MRI
timeFrame: 78 weeks
Other outcomes:
measure: Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite
timeFrame: 78 weeks
measure: Change in cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture
timeFrame: 78 weeks
measure: Compare the influence of Apolipoprotein E genotype on the primary and selected secondary outcomes in subjects by or for whom legally acceptable consent is separately provided
timeFrame: 78 weeks
measure: Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging
timeFrame: 78 weeks
measure: Change in expected increase in ventricular volume as measured by brain MRI
timeFrame: 78 weeks
measure: Change in expected decline in hippocampal volume as measured by brain MRI
timeFrame: 78 weeks
Locations:
city: Phoenix
country: United States
facility: Xenoscience, Inc / 21st Century Neurology
state: Arizona
city: Phoenix
country: United States
facility: NoesisPharma Clinical Trials
state: Arizona
city: Bellflower
country: United States
facility: CITrials
state: California
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Fountain Valley
country: United States
facility: Southern California Research, LLC
state: California
city: Laguna Hills
country: United States
facility: Feldman, Robert MD
state: California
city: Lemon Grove
country: United States
facility: Synergy East
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network
state: California
city: Pasadena
country: United States
facility: Neuro-Therapeutics, Inc.
state: California
city: Redlands
country: United States
facility: Anderson Clinical Research
state: California
city: San Diego
country: United States
facility: Pacific Research Network
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: Santa Monica
country: United States
facility: Neurological Research Institute
state: California
city: Sherman Oaks
country: United States
facility: Schuster Medical Research Institute
state: California
city: Denver
country: United States
facility: Mile High Research Center
state: Colorado
city: New Haven
country: United States
facility: Institute for Neurodegenerative Disorders
state: Connecticut
city: New London
country: United States
facility: Coastal Connecticut Research, LLC
state: Connecticut
city: Norwalk
country: United States
facility: Research Center for Clinical Studies, Inc
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Sarasota
country: United States
facility: The Roskamp Institute, Inc.
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Tampa
country: United States
facility: USF Health Byrd Alzheimer's Institute
state: Florida
city: The Villages
country: United States
facility: Compass Research, LLC - North Clinic
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute (Palm Beach Neurology)
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Decatur
country: United States
facility: Neurostudies.net
state: Georgia
city: Elk Grove
country: United States
facility: Alexian Brothers Neurosciences Institute
state: Illinois
city: Des Moines
country: United States
facility: Ruan Neurology Clinic and Research Center
state: Iowa
city: Rockville
country: United States
facility: CBH Health, LLC
state: Maryland
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Hattiesburg
country: United States
facility: Neurological Research Center - Hattiesburg Clinic
state: Mississippi
city: Olive Branch
country: United States
facility: Olive Branch Family Medical
state: Mississippi
city: Creve Coeur
country: United States
facility: Millennium Psychiatric Associates
state: Missouri
city: Eatontown
country: United States
facility: Memory Enhancement Centers of America, Inc
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ PC
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience
state: New Mexico
city: Albany
country: United States
facility: Neurological Associates of Albany, P. C.
state: New York
city: Elmsford
country: United States
facility: MedicalPsych Care, PLLC
state: New York
city: New York
country: United States
facility: Columbia University Taub Institute
state: New York
city: Orangeburg
country: United States
facility: Research Foundation for Mental Hygiene, Inc.
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: Clinical Trials of America, Inc
state: North Carolina
city: Canton
country: United States
facility: Neurobehavorial Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Clinical Research Center
state: Oklahoma
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Providence
country: United States
facility: RI Hospital
state: Rhode Island
city: Cordova
country: United States
facility: Neurology Clinic, P.C.
state: Tennessee
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions CNS Healthcare
state: Tennessee
city: Austin
country: United States
facility: Senior Adults Specialty Research, Inc.
state: Texas
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP
state: Texas
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
city: Waukesha
country: United States
facility: Independent Psychiatric Consultants
state: Wisconsin
city: Herston
country: Australia
facility: Discipline of Psychiatry, University of Queensland
state: Queensland
city: Bruxelles
country: Belgium
facility: University Hospital Brussels Department of Neurology
city: Gent
country: Belgium
facility: University Hospital Gent Department of Neurology
city: Hasselt
country: Belgium
facility: Jessa Hospital
city: Sint-Truiden
country: Belgium
facility: Regional Hospital Sint-Trudo
city: Wilrijk
country: Belgium
facility: GasthuisZusters Antwerpen Sint-Augustinus
city: Vancouver
country: Canada
facility: University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders
state: British Columbia
city: London
country: Canada
facility: Parkwood Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb, Department of Neurology
city: Zagreb
country: Croatia
facility: University Psychiatric Hospital Vrapče
city: Kuopio
country: Finland
facility: University of Eastern Finland, Brain Research Unit Mediteknia
city: Turku
country: Finland
facility: Clinical Research Services Turku (CRST)
city: Colmar Cedex
country: France
facility: Hôpitaux Civils de Colmar
city: Toulouse
country: France
facility: Hôpital La Grave
city: Villeurbanne
country: France
facility: Hôpital de Charpennes
city: Achim
country: Germany
facility: Neurozentrum Achim Dr. med. Andreas Mahler
city: Berlin
country: Germany
facility: University Medicine Berlin - Charité, CBF, Neurology
city: Berlin
country: Germany
facility: Memory Clinic, ECRC
city: Leipzig
country: Germany
facility: Arzeneimittelforschung Leipzig GmbH
city: Rostock
country: Germany
facility: Klinik und Poliklinik für Psychiatrie und Psychotherapie Zentrum für Nervenheilkunde - Universitätsklinikum Rostock
city: Ancona
country: Italy
facility: A.O.U. Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi
city: Brescia
country: Italy
facility: IRCCS San Giovanni di Dio - Fatebenefratelli
city: Chieti Scalo
country: Italy
facility: Fondazione Universita 'G. D'Annunzio di Chieti
city: Genova
country: Italy
facility: Clinical Neurology Department of Neuroscience (DINOGMI) - University of Genoa
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Sant'Andrea di Roma - Unita' di Neurologia
city: Rotterdam
country: Netherlands
facility: Alzheimer Center Southwest Netherlands, Erasmus MC
city: Barcelona
country: Spain
facility: Fundacio ACE
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Terrassa
country: Spain
facility: Hospital Universitari Mútua de Terrassa
city: Aberdeen
country: United Kingdom
facility: Grampian NHS, Royal Cornhill Hospital
city: Crowborough
country: United Kingdom
facility: Sussex Partnership NHS Foundation Trust, Cognitive Treatment and Research Unit
city: London
country: United Kingdom
facility: Re:Cogniton Health
city: Southampton
country: United Kingdom
facility: Memory Assessment and Research Centre (MARC)
city: Swindon
country: United Kingdom
facility: Kingshill Research Centre, Victoria Hospital
Study officials:
References: