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

Sponsor

TauRx Therapeutics Ltd (Industry)

Overall Status

Completed

CT.gov ID

NCT01689246

Collaborator

(none)

891

Enrollment

121

Locations

Arms

Duration (Months)

7.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: TRx0237 150 mg/day Drug: TRx0237 250 mg/day Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

891 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Nov 1, 2015

Actual Study Completion Date :

Nov 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TRx0237 250 mg/day	Drug: TRx0237 250 mg/day TRx0237 125 mg tablets will be administered twice daily.
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 150 mg/day	Drug: TRx0237 150 mg/day TRx0237 75 mg tablets will be administered twice daily.

Arm

Intervention/Treatment

Experimental: TRx0237 250 mg/day

Drug: TRx0237 250 mg/day

TRx0237 125 mg tablets will be administered twice daily.

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 150 mg/day

Drug: TRx0237 150 mg/day

TRx0237 75 mg tablets will be administered twice daily.

Outcome Measures

Primary Outcome Measures

Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) [65 weeks]
Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) [65 weeks]
Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [65 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 suicide and self-harm, brain magnetic resonance imaging (MRI), and potential for serotonin toxicity

Secondary Outcome Measures

Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [65 weeks]
Change from Baseline on Mini-Mental Status Examination (MMSE) [65 weeks]
Change in expected decline of whole brain volume as measured by brain MRI [39 weeks and 65 weeks]

Other Outcome Measures

Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging [39 weeks and 65 weeks]
Change in expected increase in ventricular volume and decline in hippocampal volume as evaluated by MRI [39 weeks and 65 weeks]
Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite [65 weeks]
Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture [65 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 [65 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 89 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xenoscience, Inc/ 21st Century Neurology	Phoenix	Arizona	United States	85004
2	Feldman, Robert MD	Laguna Hills	California	United States	92653
3	University of Southern California	Los Angeles	California	United States	90033
4	Shankle Clinic and Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92658
5	Pacific Research Network	San Diego	California	United States	92103
6	San Francisco Clinical Research Center	San Francisco	California	United States	94118
7	Yale University School of Medicine	New Haven	Connecticut	United States	06510
8	JEM Research	Atlantis	Florida	United States	33462
9	Brain Matters Research	Delray Beach	Florida	United States	33445
10	CNS Healthcare, Inc	Jacksonville	Florida	United States	32256
11	Compass Research, LLC-North Clinic	Leesburg	Florida	United States	34748
12	Miami Research Associates	Miami	Florida	United States	33143
13	Compass Research, LLC	Orlando	Florida	United States	32806
14	iResearch Atlanta	Decatur	Georgia	United States	30030
15	Alexian Brothers Neurosciences Institute	Elk Grove	Illinois	United States	60007
16	ActivMed Practices & Research	Methuen	Massachusetts	United States	01844
17	Olive Branch Family Medical	Olive Branch	Mississippi	United States	38654
18	Memory Enhancement Centers of America, Inc	Eatontown	New Jersey	United States	07724
19	CRI Worldwide	Marlton	New Jersey	United States	08053
20	The Cognitive Research Center of New Jersey	Springfield	New Jersey	United States	07801
21	Advanced Memory Research Institute of NJ PC	Toms River	New Jersey	United States	08757
22	Neurological Associates of Albany, P. C.	Albany	New York	United States	12208
23	SPRI	Brooklyn	New York	United States	11235
24	Neurobehavioral Clinical Research	Canton	Ohio	United States	44718
25	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
26	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
27	Division of Rehabilitation and Aged Care	Hornsby	New South Wales	Australia	2077
28	Southern Neurology Pty Limited	Kogarah	New South Wales	Australia	2217
29	Academic Department for Old Age Psychiatry, Prince of Wales Hospital	Randwick	New South Wales	Australia	2031
30	Discipline of Psychiatry, University of Qld	Herston	Queensland	Australia	4006
31	Royal Adelaide Hospital Memory Trials Centre	Adelaide	South Australia	Australia	5000
32	Memory Unit, Neurology, The Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
33	Medical and Cognitive Research Unit, Austin Health Heidelberg Repatriation Hospital	Heidelberg West	Victoria	Australia	3081
34	McCusker Alzheimer's Research Foundation Inc	Nedlands	Western Australia	Australia	6009
35	Neurodegenerative Disorders Research Pty Ltd	Perth	Western Australia	Australia	6005
36	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	1431
37	UMHAT "Alexandrovska" Clinic of Psychiatry First Department of Psychiatry	Sofia		Bulgaria	1431
38	Okanagan Clinical Trials	Kelowna	British Columbia	Canada	V1Y 1Z9
39	True North Clinical Research Kentville Inc	Kentville	Nova Scotia	Canada	B4N 4K9
40	Toronto Memory Program	North York	Ontario	Canada	M3B 2S7
41	University Hospital Centre Zagreb	Zagreb		Croatia	10000
42	University Psychiatric Hospital Vrapce	Zagreb		Croatia	10090
43	Neurozentrum Achim Dr. med. Andreas Mahler	Achim		Germany	28832
44	Charité, University Medicine Berlin, CBF, Neurology	Berlin		Germany	12200
45	Memory Clinic, ECRC	Berlin		Germany	13125
46	Neurologia Ospedale Maggiore Policlinico	Milano		Italy	20122
47	Istituto Neurologico Carlo Besta	Milano		Italy	20133
48	IRCCS Istituto neurologico Casimiro Mondino	Pavia		Italy	27100
49	Clinica Neurologica, Università di Perugia-Ospedale S. Maria della Misericordia	Perugia		Italy	06156
50	Universita' Cattolica del Sacro Cuore	Roma		Italy	00168
51	Azienda Ospedaliera Universitaria Sant'Andrea di Roma- Unita' di Neurologia	Roma		Italy	00189
52	Dipartimento di Neuroscienze Universita' di Torino	Torino		Italy	10126
53	Azienda Ospedaliera S.maria Della Misericordia	Udine		Italy	33100
54	U.O. Di Neurologia Ospedale di Circolo e Fondazione Macchi	Varese		Italy	21100
55	Dong-A Medical Center	Busan		Korea, Republic of	602-715
56	Inha University Hospital	Incheon		Korea, Republic of	400-711
57	Gachon University Gil Medical Center	Incheon		Korea, Republic of	405-760
58	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of	463-707
59	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
60	Samsung Medical Center	Seoul		Korea, Republic of	135-710
61	Asan Medical Center	Seoul		Korea, Republic of	138-736
62	Inje University Sanggye Paik Hospital	Seoul		Korea, Republic of	139-707
63	Konkuk University Medical Center	Seoul		Korea, Republic of	143-729
64	Seoul National University Boramae Medical Center	Seoul		Korea, Republic of	156-707
65	University Kuala Lumpur Royal College of Medicine	Ipoh		Malaysia	30450
66	Hospital Sultan Ismail	Johor Bahru		Malaysia	81100
67	University Malaya Medical Centre	Kuala Lumpur		Malaysia	50603
68	Taiping Hospital	Taiping		Malaysia	34000
69	Podlaskie Centrum Psychogeriatrii	Białystok		Poland	15-756
70	Pallmed sp zoo prowadząca NZOZ Dom Sue Ryder; Centrum Psychoneurologii Wieku Podeszłego	Bydgoszcz		Poland	85-796
71	NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS	Katowice		Poland	40-123
72	Gabinet Neurologiczny, Indywidualna Specjalistyczna Praktyka Lekarska	Mosina		Poland	62-050
73	NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Lekarzy	Poznań		Poland	61-853
74	Euromedis Sp. z o.o.	Szczecin		Poland	70-111
75	Usługi Lekarskie Sp.c Palasik, Żabierek	Warszawa		Poland	00-669
76	mMED	Warszawa		Poland	01-697
77	MTZ Clinical Research Sp. z o.o.	Warszawa		Poland	02-106
78	County Emergency Clinical Hospital Arad, Psychiatry Department	Arad		Romania	310022
79	CMDTA "Neomed"	Brasov		Romania	500283
80	University Emergency Central Military Hospital "Dr.Carol Davila", Psychiatry Department	Bucharest		Romania	010816
81	Psychomedical Consult	Bucharest		Romania	024072
82	Clinical Municipal Hospital "Dr. Gavril Curteanu", Psychiatry Department	Oradea		Romania	410154
83	Psychiatry Hospital "Dr. Gheorghe Preda", Center of Mental Health	Sibiu		Romania	550082
84	Psychiatry Hospital "Dr. Gheorghe Preda", Department of Psychiatry III	Sibiu		Romania	550082
85	Emergency Clinical County Hospital Sibiu, Neurology Department	Sibiu		Romania	550166
86	State Budgetary Healthcare Institution of Sverdlovsk region "Sverdlovsk Regional Clinical Psychiatric Hospital"	Ekaterinburg		Russian Federation	620030
87	Non-governmental Healthcare Institution "Central Clinical Hospital #6 of the JSC "Russian Railways"	Moscow		Russian Federation	109388
88	Mental Health Research Center of the Russian Academy of Medical Sciences, Gerontopsychiatry department	Moscow		Russian Federation	115522
89	Mental Health Research Center of the Russian Academy of Medical Sciences	Moscow		Russian Federation	115522
90	CityClinical Hospital #34, City Scientific Practical Neurological Center	Novosibirsk		Russian Federation	630054
91	City Geriatric Medical and Social Center	Saint Petersburg		Russian Federation	190103
92	Saint Nicholas Psychiatric Hospital	Saint Petersburg		Russian Federation	190121
93	Saint Petersburg Psychoneurological Research Institute n. a. V.M. Bekhterev	Saint Petersburg		Russian Federation	192019
94	National University Hospital (NUH)	Singapore		Singapore	119223
95	National Neuroscience Institute (NNI)	Singapore		Singapore	308433
96	Tan Tock Seng Hospital (TTSH)	Singapore		Singapore	308433
97	Changi General Hospital	Singapore		Singapore	529889
98	Hospital Universitario de Ceuta	Ceuta		Spain	51003
99	Hospital Reina Sofía	Córdoba		Spain	14011
100	Hospital Clinico San Carlos	Madrid		Spain	28040
101	Hospital Viamed Montecanal	Zaragoza		Spain	50006
102	Changhua Christian Hospital	Changhua		Taiwan
103	Chang Gung Memorial Hospital, Kaohsiung	Kaohsiung		Taiwan
104	China Medical University Hospital	Taichung		Taiwan
105	En Chu Kong Hospital	Taipei		Taiwan
106	National Taiwan University Hospital	Taipei		Taiwan
107	National Yang-Ming University School of Medicine	Taipei		Taiwan
108	Chang Gung Memorial Hospital, Linkou	Taoyuan		Taiwan
109	NHS Grampian, Department of Old Age Psychiatry Royal Cornhill Hospital	Aberdeen		United Kingdom	AB25 2ZH
110	RICE - The Research Institute for the Care of Older People	Bath		United Kingdom	BA1 3NG
111	Belfast Health and Social Care Trust (BHSCT)	Belfast		United Kingdom	BT12 6BA
112	The Barberry Centre	Birmingham		United Kingdom	B15 2SG
113	MAC Clinical Research Ltd	Blackpool		United Kingdom	FY2 0JH
114	MAC Clinical Research Ltd	Bradford		United Kingdom	BD3 0DQ
115	MAC Clinical Research Ltd	Cannock		United Kingdom	WS11 0BN
116	MAC Clinical Research Ltd	Leeds		United Kingdom	LS10 1DU
117	Re: Cognition Health Ltd.	London		United Kingdom	W1G 9JF
118	Charing Cross Hospital	London		United Kingdom	W6 8RF
119	Dementia Research Centre	London		United Kingdom	WC1N 3BG
120	MAC Clinical Research Ltd	Manchester		United Kingdom	M13 9NQ
121	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD