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

Alzheimer's Disease Clinical Trial

Official title:

Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 15-Month Trial of TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01689246
• Other study ID #: TRx-237-015
• Status: Completed
• Phase: Phase 3
• First received: September 14, 2012
• Last updated: March 12, 2018
• Start date: January 2013
• Est. completion date: November 2015

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 to moderate Alzheimer's Disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 891
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• 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 1 (mild) to 2 (moderate) and MMSE score of 14-26 (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, or 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:

• 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 about methemoglobinemia at approved doses

• Current or prior participation in a clinical trial as follows:

• Clinical trial of a product for cognition within 3 months of Screening (unless confirmed to have been randomized to placebo)

• A clinical trial of a drug, biologic, therapeutic 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 150 mg/day
TRx0237 75 mg tablets will be administered twice daily.
• TRx0237 250 mg/day
TRx0237 125 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	Royal Adelaide Hospital Memory Trials Centre	Adelaide	South Australia
Australia	Medical and Cognitive Research Unit, Austin Health Heidelberg Repatriation Hospital	Heidelberg West	Victoria
Australia	Discipline of Psychiatry, University of Qld	Herston	Queensland
Australia	Division of Rehabilitation and Aged Care	Hornsby	New South Wales
Australia	Southern Neurology Pty Limited	Kogarah	New South Wales
Australia	McCusker Alzheimer's Research Foundation Inc	Nedlands	Western Australia
Australia	Neurodegenerative Disorders Research Pty Ltd	Perth	Western Australia
Australia	Academic Department for Old Age Psychiatry, Prince of Wales Hospital	Randwick	New South Wales
Australia	Memory Unit, Neurology, The Queen Elizabeth Hospital	Woodville South	South Australia
Bulgaria	UMHAT "Alexandrovska" Clinic of Neurology Diseases Department of Neurodegenerative and Immune and Infectious Diseases of Central Nervous System with Sector for Treatment of Neuroinfections	Sofia
Bulgaria	UMHAT "Alexandrovska" Clinic of Psychiatry First Department of Psychiatry	Sofia
Canada	Okanagan Clinical Trials	Kelowna	British Columbia
Canada	True North Clinical Research Kentville Inc	Kentville	Nova Scotia
Canada	Toronto Memory Program	North York	Ontario
Croatia	University Hospital Centre Zagreb	Zagreb
Croatia	University Psychiatric Hospital Vrapce	Zagreb
Germany	Neurozentrum Achim Dr. med. Andreas Mahler	Achim
Germany	Charité, University Medicine Berlin, CBF, Neurology	Berlin
Germany	Memory Clinic, ECRC	Berlin
Italy	Istituto Neurologico Carlo Besta	Milano
Italy	Neurologia Ospedale Maggiore Policlinico	Milano
Italy	IRCCS Istituto neurologico Casimiro Mondino	Pavia
Italy	Clinica Neurologica, Università di Perugia-Ospedale S. Maria della Misericordia	Perugia
Italy	Azienda Ospedaliera Universitaria Sant'Andrea di Roma- Unita' di Neurologia	Roma
Italy	Universita' Cattolica del Sacro Cuore	Roma
Italy	Dipartimento di Neuroscienze Universita' di Torino	Torino
Italy	Azienda Ospedaliera S.maria Della Misericordia	Udine
Italy	U.O. Di Neurologia Ospedale di Circolo e Fondazione Macchi	Varese
Korea, Republic of	Dong-A Medical Center	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Inje University Sanggye Paik Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Boramae Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Malaysia	University Kuala Lumpur Royal College of Medicine	Ipoh
Malaysia	Hospital Sultan Ismail	Johor Bahru
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Taiping Hospital	Taiping
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok
Poland	Pallmed sp zoo prowadzaca NZOZ Dom Sue Ryder; Centrum Psychoneurologii Wieku Podeszlego	Bydgoszcz
Poland	NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS	Katowice
Poland	Gabinet Neurologiczny, Indywidualna Specjalistyczna Praktyka Lekarska	Mosina
Poland	NZOZ Neuro-Kard Ilkowski i Partnerzy Spólka Partnerska Lekarzy	Poznan
Poland	Euromedis Sp. z o.o.	Szczecin
Poland	mMED	Warszawa
Poland	MTZ Clinical Research Sp. z o.o.	Warszawa
Poland	Uslugi Lekarskie Sp.c Palasik, Zabierek	Warszawa
Romania	County Emergency Clinical Hospital Arad, Psychiatry Department	Arad
Romania	CMDTA "Neomed"	Brasov
Romania	Psychomedical Consult	Bucharest
Romania	University Emergency Central Military Hospital "Dr.Carol Davila", Psychiatry Department	Bucharest
Romania	Clinical Municipal Hospital "Dr. Gavril Curteanu", Psychiatry Department	Oradea
Romania	Emergency Clinical County Hospital Sibiu, Neurology Department	Sibiu
Romania	Psychiatry Hospital "Dr. Gheorghe Preda", Center of Mental Health	Sibiu
Romania	Psychiatry Hospital "Dr. Gheorghe Preda", Department of Psychiatry III	Sibiu
Russian Federation	State Budgetary Healthcare Institution of Sverdlovsk region "Sverdlovsk Regional Clinical Psychiatric Hospital"	Ekaterinburg
Russian Federation	Mental Health Research Center of the Russian Academy of Medical Sciences	Moscow
Russian Federation	Mental Health Research Center of the Russian Academy of Medical Sciences, Gerontopsychiatry department	Moscow
Russian Federation	Non-governmental Healthcare Institution "Central Clinical Hospital #6 of the JSC "Russian Railways"	Moscow
Russian Federation	CityClinical Hospital #34, City Scientific Practical Neurological Center	Novosibirsk
Russian Federation	City Geriatric Medical and Social Center	Saint Petersburg
Russian Federation	Saint Nicholas Psychiatric Hospital	Saint Petersburg
Russian Federation	Saint Petersburg Psychoneurological Research Institute n. a. V.M. Bekhterev	Saint Petersburg
Singapore	Changi General Hospital	Singapore
Singapore	National Neuroscience Institute (NNI)	Singapore
Singapore	National University Hospital (NUH)	Singapore
Singapore	Tan Tock Seng Hospital (TTSH)	Singapore
Spain	Hospital Universitario de Ceuta	Ceuta
Spain	Hospital Reina Sofía	Córdoba
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Viamed Montecanal	Zaragoza
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	Chang Gung Memorial Hospital, Kaohsiung	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	En Chu Kong Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	National Yang-Ming University School of Medicine	Taipei
Taiwan	Chang Gung Memorial Hospital, Linkou	Taoyuan
United Kingdom	NHS Grampian, Department of Old Age Psychiatry Royal Cornhill Hospital	Aberdeen
United Kingdom	RICE - The Research Institute for the Care of Older People	Bath
United Kingdom	Belfast Health and Social Care Trust (BHSCT)	Belfast
United Kingdom	The Barberry Centre	Birmingham
United Kingdom	MAC Clinical Research Ltd	Blackpool
United Kingdom	MAC Clinical Research Ltd	Bradford
United Kingdom	MAC Clinical Research Ltd	Cannock
United Kingdom	MAC Clinical Research Ltd	Leeds
United Kingdom	Charing Cross Hospital	London
United Kingdom	Dementia Research Centre	London
United Kingdom	Re: Cognition Health Ltd.	London
United Kingdom	MAC Clinical Research Ltd	Manchester
United Kingdom	Southampton General Hospital	Southampton
United States	Neurological Associates of Albany, P. C.	Albany	New York
United States	JEM Research	Atlantis	Florida
United States	FutureSearch Trials of Neurology	Austin	Texas
United States	SPRI	Brooklyn	New York
United States	Neurobehavioral Clinical Research	Canton	Ohio
United States	iResearch Atlanta	Decatur	Georgia
United States	Brain Matters Research	Delray Beach	Florida
United States	Memory Enhancement Centers of America, Inc	Eatontown	New Jersey
United States	Alexian Brothers Neurosciences Institute	Elk Grove	Illinois
United States	CNS Healthcare, Inc	Jacksonville	Florida
United States	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	Feldman, Robert MD	Laguna Hills	California
United States	Compass Research, LLC-North Clinic	Leesburg	Florida
United States	University of Southern California	Los Angeles	California
United States	CRI Worldwide	Marlton	New Jersey
United States	ActivMed Practices & Research	Methuen	Massachusetts
United States	Miami Research Associates	Miami	Florida
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Shankle Clinic and Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Olive Branch Family Medical	Olive Branch	Mississippi
United States	Compass Research, LLC	Orlando	Florida
United States	Xenoscience, Inc/ 21st Century Neurology	Phoenix	Arizona
United States	Pacific Research Network	San Diego	California
United States	San Francisco Clinical Research Center	San Francisco	California
United States	The Cognitive Research Center of New Jersey	Springfield	New Jersey
United States	Advanced Memory Research Institute of NJ PC	Toms River	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
TauRx Therapeutics Ltd

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Croatia,  Germany,  Italy,  Korea, Republic of,  Malaysia,  Poland,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging		39 weeks and 65 weeks
Other	Change in expected increase in ventricular volume and decline in hippocampal volume as evaluated by MRI		39 weeks and 65 weeks
Other	Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite		65 weeks
Other	Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture		65 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		65 weeks
Primary	Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)		65 weeks
Primary	Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)		65 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 suicide and self-harm, brain magnetic resonance imaging (MRI), and potential for serotonin toxicity	65 weeks
Secondary	Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)		65 weeks
Secondary	Change from Baseline on Mini-Mental Status Examination (MMSE)		65 weeks
Secondary	Change in expected decline of whole brain volume as measured by brain MRI		39 weeks and 65 weeks

External Links

•   Alzheimer's Survey