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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01689233
• Other study ID #: TRx-237-005
• Status: Completed
• Phase: Phase 3
• First received: September 14, 2012
• Last updated: March 12, 2018
• Start date: October 2012
• Est. completion date: May 2016

Study information

• Verified date: March 2018
• Source: TauRx Therapeutics Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 800
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 89 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• TRx0237 200 mg/day
TRx0237 100 mg tablets will be administered twice daily.
• 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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
TauRx Therapeutics Ltd

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Croatia,  Finland,  France,  Germany,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite		78 weeks
Other	Change in cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture		78 weeks
Other	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
Other	Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging		78 weeks
Other	Change in expected increase in ventricular volume as measured by brain MRI		78 weeks
Other	Change in expected decline in hippocampal volume as measured by brain MRI		78 weeks
Primary	Change from Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)		78 weeks
Primary	Change from Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)		78 weeks
Primary	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	Change from Baseline in Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)		78 weeks
Secondary	Change from Baseline in Mini-Mental Status Examination (MMSE)		78 weeks
Secondary	Change from Baseline in Neuropsychiatric Inventory (NPI)		78 weeks
Secondary	Change from Baseline in Montgomery-Asberg Depression Rating Scale (MADRS)		78 weeks
Secondary	Change in expected decline of whole brain volume as measured by brain MRI		78 weeks

External Links

•   Alzheimer's Survey