Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild Alzheimer's Disease

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 18-Month Safety and Efficacy Study of TRx0237 in Subjects With Mild Alzheimer's Disease

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

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: TRx0237 200 mg/day; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 800
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Discipline of Psychiatry, University of Queensland
• Belgium
  • Bruxelles, Belgium, 1090
    • University Hospital Brussels Department of Neurology
  • Gent, Belgium, 9000
    • University Hospital Gent Department of Neurology
  • Hasselt, Belgium, 3500
    • Jessa Hospital
  • Sint-Truiden, Belgium, 3800
    • Regional Hospital Sint-Trudo
  • Wilrijk, Belgium, 2610
    • GasthuisZusters Antwerpen Sint-Augustinus
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z3
      • University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders
  • Ontario
    • London, Ontario, Canada, N6C 0A7
      • Parkwood Institute
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Croatia
  • Zagreb, Croatia, 10000
    • University Hospital Centre Zagreb, Department of Neurology
  • Zagreb, Croatia, 10090
    • University Psychiatric Hospital Vrapce
• Finland
  • Kuopio, Finland, 70210
    • University of Eastern Finland, Brain Research Unit Mediteknia
  • Turku, Finland, 20520
    • Clinical Research Services Turku (CRST)
• France
  • Colmar Cedex, France, 68024
    • Hôpitaux Civils de Colmar
  • Toulouse, France, 31059
    • Hôpital La Grave
  • Villeurbanne, France, 69100
    • Hôpital de Charpennes
• Germany
  • Achim, Germany, 28832
    • Neurozentrum Achim Dr. med. Andreas Mahler
  • Berlin, Germany, 13125
    • Memory Clinic, ECRC
  • Berlin, Germany, 12200
    • University Medicine Berlin - Charité, CBF, Neurology
  • Leipzig, Germany, 04107
    • Arzeneimittelforschung Leipzig GmbH
  • Rostock, Germany, 18147
    • Klinik und Poliklinik für Psychiatrie und Psychotherapie Zentrum für Nervenheilkunde - Universitätsklinikum Rostock
• Italy
  • Ancona, Italy, 60126
    • A.O.U. Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi
  • Brescia, Italy, 25125
    • IRCCS San Giovanni di Dio - Fatebenefratelli
  • Chieti Scalo, Italy, 66100
    • Fondazione Universita 'G. D'Annunzio di Chieti
  • Genova, Italy, 16132
    • Clinical Neurology Department of Neuroscience (DINOGMI) - University of Genoa
  • Roma, Italy, 00189
    • Azienda Ospedaliera Universitaria Sant'Andrea di Roma - Unita' di Neurologia
• Netherlands
  • Rotterdam, Netherlands, 3015
    • Alzheimer Center Southwest Netherlands, Erasmus MC
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08028
    • Fundació ACE
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Terrassa, Spain, 08221
    • Hospital Universitari Mutua de Terrassa
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZH
    • Grampian NHS, Royal Cornhill Hospital
  • Crowborough, United Kingdom, TN6 1HB
    • Sussex Partnership NHS Foundation Trust, Cognitive Treatment and Research Unit
  • London, United Kingdom, W1G 9JF
    • Re:Cogniton Health
  • Southampton, United Kingdom, SO30 3JB
    • Memory Assessment and Research Centre (MARC)
  • Swindon, United Kingdom, SN3 6BW
    • Kingshill Research Centre, Victoria Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Xenoscience, Inc / 21st Century Neurology
    • Phoenix, Arizona, United States, 85032
      • NoesisPharma Clinical Trials
  • California
    • Bellflower, California, United States, 90706
      • CiTrials
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Fountain Valley, California, United States, 92708
      • Southern California Research, LLC
    • Laguna Hills, California, United States, 92653
      • Feldman, Robert MD
    • Lemon Grove, California, United States, 91945
      • Synergy East
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network
    • Pasadena, California, United States, 91105
      • Neuro-Therapeutics, Inc.
    • Redlands, California, United States, 92374
      • Anderson Clinical Research
    • San Diego, California, United States, 92103
      • Pacific Research Network
    • San Francisco, California, United States, 94118
      • San Francisco Clinical Research Center
    • Santa Monica, California, United States, 90404
      • Neurological Research Institute
    • Sherman Oaks, California, United States, 91403
      • Schuster Medical Research Institute
  • Colorado
    • Denver, Colorado, United States, 80218
      • Mile High Research Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Institute for Neurodegenerative Disorders
    • New London, Connecticut, United States, 06320
      • Coastal Connecticut Research, LLC
    • Norwalk, Connecticut, United States, 06851
      • Research Center for Clinical Studies, Inc
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Brooksville, Florida, United States, 34601
      • Meridien Research
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Lake Worth, Florida, United States, 33449
      • Alzheimer's Research and Treatment Center
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Sarasota, Florida, United States, 34243
      • The Roskamp Institute, Inc.
    • Tampa, Florida, United States, 33613
      • USF Health Byrd Alzheimer's Institute
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
    • The Villages, Florida, United States, 32162
      • Compass Research, LLC - North Clinic
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute (Palm Beach Neurology)
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Decatur, Georgia, United States, 30033
      • Neurostudies.net
  • Illinois
    • Elk Grove, Illinois, United States, 60007
      • Alexian Brothers Neurosciences Institute
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Ruan Neurology Clinic and Research Center
  • Maryland
    • Rockville, Maryland, United States, 20850
      • CBH Health, LLC
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Quest Research Institute
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Neurological Research Center - Hattiesburg Clinic
    • Olive Branch, Mississippi, United States, 38654
      • Olive Branch Family Medical
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Millennium Psychiatric Associates
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Centers of America, Inc
    • Toms River, New Jersey, United States, 08757
      • Advanced Memory Research Institute of NJ PC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany, P. C.
    • Elmsford, New York, United States, 10523
      • MedicalPsych Care, PLLC
    • New York, New York, United States, 10032
      • Columbia University Taub Institute
    • Orangeburg, New York, United States, 10962
      • Research Foundation for Mental Hygiene, Inc.
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
    • Winston-Salem, North Carolina, United States, 27103
      • Clinical Trials of America, Inc
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neurobehavorial Clinical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Oklahoma Clinical Research Center
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
      • The Clinical Trial Center, LLC
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • RI Hospital
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, P.C.
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions CNS Healthcare
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research, Inc.
    • Dallas, Texas, United States, 75231
      • FutureSearch Trials of Dallas, LP
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • PRA Health Sciences
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • Independent Psychiatric Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 89 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo tablets will be administered twice daily. The active 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.
Experimental: TRx0237 200 mg/day	Drug: TRx0237 200 mg/day; TRx0237 100 mg tablets will be administered twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)		78 weeks
Change from Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)		78 weeks
Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes	Safety parameters include adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, potential for serotonin toxicity, brain magnetic resonance imaging (MRI), and potential for suicide or self-harm.	78 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)	78 weeks
Change from Baseline in Mini-Mental Status Examination (MMSE)	78 weeks
Change from Baseline in Neuropsychiatric Inventory (NPI)	78 weeks
Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS)	78 weeks
Change in expected decline of whole brain volume as measured by brain MRI	78 weeks

Other Outcome Measures

Outcome Measure	Time Frame
Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite	78 weeks
Change in cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture	78 weeks
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	78 weeks
Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging	78 weeks
Change in expected increase in ventricular volume as measured by brain MRI	78 weeks
Change in expected decline in hippocampal volume as measured by brain MRI	78 weeks

Collaborators and Investigators

• Sponsor: TauRx Therapeutics Ltd

Publications and helpful links

Helpful Links

• Alzheimer's Survey

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: September 14, 2012
• First Submitted That Met QC Criteria: September 20, 2012
• First Posted (Estimate): September 21, 2012

Study Record Updates

• Last Update Posted (Actual): March 14, 2018
• Last Update Submitted That Met QC Criteria: March 12, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Dementia; Alzheimer Disease; Neurodegenerative Diseases; AD; Brain Diseases; TRx0237
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: TRx-237-005