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

Phase 3

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: TRx0237 200 mg/day
Drug: Placebo

Registration Number: NCT01689233

Lead Sponsor: TauRx Therapeutics Ltd

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 800

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TRx0237 200 mg/day	TRx0237 200 mg/day	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
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	78 weeks	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.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (95): Discipline of Psychiatry, University of Queensland
🇦🇺
Herston, Queensland, Australia
Brain Matters Research
🇺🇸
Delray Beach, Florida, United States
The Roskamp Institute, Inc.
🇺🇸
Sarasota, Florida, United States
Premiere Research Institute (Palm Beach Neurology)
🇺🇸
West Palm Beach, Florida, United States
Atlanta Center for Medical Research
🇺🇸
Atlanta, Georgia, United States
Coastal Connecticut Research, LLC
🇺🇸
New London, Connecticut, United States
JEM Research
🇺🇸
Atlantis, Florida, United States
Southern California Research, LLC
🇺🇸
Fountain Valley, California, United States
CBH Health, LLC
🇺🇸
Rockville, Maryland, United States
Quest Research Institute
🇺🇸
Farmington Hills, Michigan, United States
Neurobehavorial Clinical Research
🇺🇸
Canton, Ohio, United States
Independent Psychiatric Consultants
🇺🇸
Waukesha, Wisconsin, United States
University Hospital Centre Zagreb, Department of Neurology
🇭🇷
Zagreb, Croatia
Jessa Hospital
🇧🇪
Hasselt, Belgium
Meridien Research
🇺🇸
Brooksville, Florida, United States
University of Eastern Finland, Brain Research Unit Mediteknia
🇫🇮
Kuopio, Finland
MD Clinical
🇺🇸
Hallandale Beach, Florida, United States
A.O.U. Ospedali Riuniti Umberto I - G.M. Lancisi - G. Salesi
🇮🇹
Ancona, Italy
Advanced Memory Research Institute of NJ PC
🇺🇸
Toms River, New Jersey, United States
Toronto Memory Program
🇨🇦
Toronto, Ontario, Canada
University Medicine Berlin - Charité, CBF, Neurology
🇩🇪
Berlin, Germany
RI Hospital
🇺🇸
Providence, Rhode Island, United States
University Psychiatric Hospital Vrapče
🇭🇷
Zagreb, Croatia
GasthuisZusters Antwerpen Sint-Augustinus
🇧🇪
Wilrijk, Belgium
IRCCS San Giovanni di Dio - Fatebenefratelli
🇮🇹
Brescia, Italy
Fondazione Universita 'G. D'Annunzio di Chieti
🇮🇹
Chieti Scalo, Italy
Clinical Neurology Department of Neuroscience (DINOGMI) - University of Genoa
🇮🇹
Genova, Italy
Columbia University Taub Institute
🇺🇸
New York, New York, United States
FutureSearch Trials of Dallas, LP
🇺🇸
Dallas, Texas, United States
University Hospital Brussels Department of Neurology
🇧🇪
Bruxelles, Belgium
Hospital Universitari Vall d'Hebron
🇪🇸
Barcelona, Spain
Hôpital de Charpennes
🇫🇷
Villeurbanne, France
Neurozentrum Achim Dr. med. Andreas Mahler
🇩🇪
Achim, Germany
Memory Clinic, ECRC
🇩🇪
Berlin, Germany
Hôpital La Grave
🇫🇷
Toulouse, France
University Hospital Gent Department of Neurology
🇧🇪
Gent, Belgium
Alzheimer Center Southwest Netherlands, Erasmus MC
🇳🇱
Rotterdam, Netherlands
Oklahoma Clinical Research Center
🇺🇸
Oklahoma City, Oklahoma, United States
PRA Health Sciences
🇺🇸
Salt Lake City, Utah, United States
Xenoscience, Inc / 21st Century Neurology
🇺🇸
Phoenix, Arizona, United States
San Francisco Clinical Research Center
🇺🇸
San Francisco, California, United States
Pacific Research Network
🇺🇸
San Diego, California, United States
Azienda Ospedaliera Universitaria Sant'Andrea di Roma - Unita' di Neurologia
🇮🇹
Roma, Italy
Clinical Research Services Turku (CRST)
🇫🇮
Turku, Finland
Mile High Research Center
🇺🇸
Denver, Colorado, United States
CITrials
🇺🇸
Bellflower, California, United States
NoesisPharma Clinical Trials
🇺🇸
Phoenix, Arizona, United States
Neuro-Therapeutics, Inc.
🇺🇸
Pasadena, California, United States
Synergy East
🇺🇸
Lemon Grove, California, United States
Neurological Research Institute
🇺🇸
Santa Monica, California, United States
Schuster Medical Research Institute
🇺🇸
Sherman Oaks, California, United States
Ruan Neurology Clinic and Research Center
🇺🇸
Des Moines, Iowa, United States
Memory Enhancement Centers of America, Inc
🇺🇸
Eatontown, New Jersey, United States
Research Foundation for Mental Hygiene, Inc.
🇺🇸
Orangeburg, New York, United States
Neurology Clinic, P.C.
🇺🇸
Cordova, Tennessee, United States
Clinical Neuroscience Solutions CNS Healthcare
🇺🇸
Memphis, Tennessee, United States
University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders
🇨🇦
Vancouver, British Columbia, Canada
Parkwood Institute
🇨🇦
London, Ontario, Canada
Regional Hospital Sint-Trudo
🇧🇪
Sint-Truiden, Belgium
Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
Hôpitaux Civils de Colmar
🇫🇷
Colmar Cedex, France
Hospital Universitari Mútua de Terrassa
🇪🇸
Terrassa, Spain
Sussex Partnership NHS Foundation Trust, Cognitive Treatment and Research Unit
🇬🇧
Crowborough, United Kingdom
Neurostudies.net
🇺🇸
Decatur, Georgia, United States
ATP Clinical Research, Inc.
🇺🇸
Costa Mesa, California, United States
Feldman, Robert MD
🇺🇸
Laguna Hills, California, United States
Research Center for Clinical Studies, Inc
🇺🇸
Norwalk, Connecticut, United States
Collaborative Neuroscience Network
🇺🇸
Long Beach, California, United States
Senior Adults Specialty Research, Inc.
🇺🇸
Austin, Texas, United States
Anderson Clinical Research
🇺🇸
Redlands, California, United States
Fundacio ACE
🇪🇸
Barcelona, Spain
Alzheimer's Research and Treatment Center
🇺🇸
Lake Worth, Florida, United States
Bradenton Research Center
🇺🇸
Bradenton, Florida, United States
Compass Research, LLC - North Clinic
🇺🇸
The Villages, Florida, United States
Millennium Psychiatric Associates
🇺🇸
Creve Coeur, Missouri, United States
Grampian NHS, Royal Cornhill Hospital
🇬🇧
Aberdeen, United Kingdom
Olive Branch Family Medical
🇺🇸
Olive Branch, Mississippi, United States
Neurological Research Center - Hattiesburg Clinic
🇺🇸
Hattiesburg, Mississippi, United States
Alexian Brothers Neurosciences Institute
🇺🇸
Elk Grove, Illinois, United States
Albuquerque Neuroscience
🇺🇸
Albuquerque, New Mexico, United States
Neurological Associates of Albany, P. C.
🇺🇸
Albany, New York, United States
Wake Research Associates
🇺🇸
Raleigh, North Carolina, United States
MedicalPsych Care, PLLC
🇺🇸
Elmsford, New York, United States
Hospital Universitario La Paz
🇪🇸
Madrid, Spain
Memory Assessment and Research Centre (MARC)
🇬🇧
Southampton, United Kingdom
Arzeneimittelforschung Leipzig GmbH
🇩🇪
Leipzig, Germany
Klinik und Poliklinik für Psychiatrie und Psychotherapie Zentrum für Nervenheilkunde - Universitätsklinikum Rostock
🇩🇪
Rostock, Germany
Kingshill Research Centre, Victoria Hospital
🇬🇧
Swindon, United Kingdom
Institute for Neurodegenerative Disorders
🇺🇸
New Haven, Connecticut, United States
Compass Research, LLC
🇺🇸
Orlando, Florida, United States
Axiom Clinical Research of Florida
🇺🇸
Tampa, Florida, United States
USF Health Byrd Alzheimer's Institute
🇺🇸
Tampa, Florida, United States
Clinical Trials of America, Inc
🇺🇸
Winston-Salem, North Carolina, United States
The Clinical Trial Center, LLC
🇺🇸
Jenkintown, Pennsylvania, United States
Re:Cogniton Health
🇬🇧
London, United Kingdom