Open-Label Study of Leuco-methylthioninium Bis(Hydromethanesulfonate) (LMTM) in Subjects With Alzheimer's Disease or Behavioral Variant Frontotemporal Dementia (bvFTD)

• Sponsor: TauRx Therapeutics Ltd (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02245568
• Collaborator: (none)
• Enrollment: 913
• Locations: 135
• Arm: 1
• Actual Duration (Months): 33
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to provide subjects who have completed participation in a Phase 2 or Phase 3 trial of LMTM continued access to therapy and to evaluate the long-term safety of LMTM.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease; Behavioral Variant Frontotemporal Dementia	Drug: LMTM	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 913 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Extension Study of the Effects of LMTM in Subjects With Alzheimer's Disease or Behavioral Variant Frontotemporal Dementia (bvFTD)
• Actual Study Start Date: Aug 1, 2014
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: LMTM

Drug: LMTM; The initial LMTM dose was 200 mg/day (one 100-mg tablet twice daily), except in subjects with bvFTD who were taking a reduced dose (i.e., 100 mg/day) upon entering this extension study. The dose could be increased (after at least 13 weeks of treatment) or decreased (at any time at or after 2 weeks of treatment) by the Investigator in 100-mg increments or decrements. The maximum allowable dose was 300 mg/day (or in those countries where limited by a Competent Authority or Ethics Committee, 200 mg/day).

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Serious or Non-serious Adverse Events [Up to 34 months]

   Study-emergent adverse events (including the onset of new adverse events or worsening of pre-existing adverse events) were recorded from the time of first dose in this study to the end of study participation. All laboratory test, vital sign, or electrocardiogram parameter abnormalities deemed clinically significant by the Investigator were to be reported as adverse events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects with all cause dementia and probable Alzheimer's disease at enrollment and who completed participation in one of the following three TauRx studies (inclusive of the 4-week post-treatment follow-up visit): TRx-237-005, TRx-237-008, or TRx-237-015.

• Subjects with a diagnosis of probable bvFTD at enrollment and who completed participation in TauRx study TRx-237-007 through Visit 9 (Week 52).

• Females, if of child-bearing potential, must practice true abstinence or continue 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 and ethics approval is/are able to read, understand, and provide written informed consent

• Has an 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 ≥1 hour/day ≥3 days/week; agrees to accompany the subject to each study visit; and is able to verify daily compliance with study drug

• Able to comply with the study procedures

Exclusion Criteria:

• History of swallowing difficulties

• Pregnant or breastfeeding

• Clinically significant laboratory, pulse co-oximetry, electrocardiogram, or imaging abnormality (in originating study) or emergent intercurrent illness that, in the judgment of the principal investigator, could result in the risk of participation outweighing the potential benefit

• Current participation in, or intent to enroll in, another clinical trial of a drug, biologic, device, or medical food

• In Germany, subjects mandated to reside in a continuous care or assisted living facility or those whose willingness to participate in the clinical trial may be unduly influenced

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xenoscience, Inc / 21st Century Neurology	Phoenix	Arizona	United States	85004
2	Southern California Research, LLC	Fountain Valley	California	United States	92708
3	Feldman, Robert MD	Laguna Hills	California	United States	92653
4	Collaborative Neuroscience Network	Long Beach	California	United States	90806
5	The Shankle Clinic	Newport Beach	California	United States	92663
6	Neuro-Therapeutics, Inc.	Pasadena	California	United States	91105
7	Pacific Research Network	San Diego	California	United States	92103
8	San Francisco Clinical Research Center	San Francisco	California	United States	94118
9	Memory and Aging Centre	San Francisco	California	United States	94158
10	Schuster Medical Research Institute	Sherman Oaks	California	United States	91403
11	Mile High Research Center	Denver	Colorado	United States	80218
12	Institute for Neurodegenerative Disorders	New Haven	Connecticut	United States	06510
13	Yale University School of Medicine	New Haven	Connecticut	United States	06510
14	Coastal Connecticut Research, LLC	New London	Connecticut	United States	06320
15	JEM Research	Atlantis	Florida	United States	33462
16	Bradenton Research Center	Bradenton	Florida	United States	34205
17	Meridien Research	Brooksville	Florida	United States	34601
18	Brain Matters Research	Delray Beach	Florida	United States	33445
19	MD Clinical	Hallandale Beach	Florida	United States	33009
20	Mayo Clinic	Jacksonville	Florida	United States	32224
21	CNS Healthcare, Inc	Jacksonville	Florida	United States	32256
22	Miami Research Associates	Miami	Florida	United States	33143
23	Compass Research, LLC	Orlando	Florida	United States	32806
24	The Roskamp Institute, Inc.	Sarasota	Florida	United States	34243
25	Axiom Clinical Research of Florida	Tampa	Florida	United States	33609
26	University of South Florida	Tampa	Florida	United States	33613
27	Compass Research, LLC - North Clinic	The Villages	Florida	United States	32162
28	iResearch Atlanta	Decatur	Georgia	United States	30030
29	Neurostudies.net	Decatur	Georgia	United States	30033
30	Alexian Brothers Neurosciences Institute	Elk Grove Village	Illinois	United States	60007
31	Ruan Neurology Clinic and Research Center	Des Moines	Iowa	United States	50314
32	ActivMed Practices & Research	Methuen	Massachusetts	United States	01844
33	Mayo Clinic, Alzheimer's Disease Research Center	Rochester	Minnesota	United States	55905
34	Neurological Research Center - Hattiesburg Clinic	Hattiesburg	Mississippi	United States	39401
35	Millennium Psychiatric Associates	Creve Coeur	Missouri	United States	63141
36	Memory Enhancement Center of America, Inc	Eatontown	New Jersey	United States	07724
37	The Atlantic Neuroscience Institute	Springfield	New Jersey	United States	07801
38	Advanced Memory Research Institute of NJ PC	Toms River	New Jersey	United States	08757
39	Neurological Associates of Albany, P. C.	Albany	New York	United States	12208
40	SPRI	Brooklyn	New York	United States	11235
41	Columbia University Taub Institute	New York	New York	United States	10032
42	Research Foundation for Mental Hygiene, Inc.	Orangeburg	New York	United States	10962
43	UNC Department of Neurology, Physicians Office Building	Chapel Hill	North Carolina	United States	27599
44	Clinical Trials of America, Inc	Winston-Salem	North Carolina	United States	27103
45	Neurobehavioral Clinical Research	Canton	Ohio	United States	44718
46	University Hospitals Case Medical Center, Neurology Clinical Trials Unit	Cleveland	Ohio	United States	44106
47	Rivus Wellness and Research Institute	Oklahoma City	Oklahoma	United States	73112
48	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
49	Hospital of the University of Pennsylvania, Department of Neurology	Philadelphia	Pennsylvania	United States	19104
50	RI Hospital	Providence	Rhode Island	United States	02903
51	Neurology Clinic, P.C.	Cordova	Tennessee	United States	38018
52	Clinical Neuroscience Solutions CNS Healthcare	Memphis	Tennessee	United States	38119
53	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
54	Senior Adults Specialty Research, Inc.	Austin	Texas	United States	78757
55	FutureSearch Trials of Dallas, LP	Dallas	Texas	United States	75231
56	University of Virginia Adult Neurology, Primary Care Center	Charlottesville	Virginia	United States	22903
57	Independent Psychiatric Consultants	Waukesha	Wisconsin	United States	53188
58	Frontotemporal Research Group	Camperdown	New South Wales	Australia	2000
59	Division of Rehabilitation and Aged Care	Hornsby	New South Wales	Australia	2077
60	Southern Neurology Pty Limited	Kogarah	New South Wales	Australia	2217
61	Discipline of Psychiatry, University of Queensland	Herston	Queensland	Australia	4006
62	Royal Adelaide Hospital Memory Trials Centre	Adelaide	South Australia	Australia	5000
63	Box Hill Hospital	Box Hill	Victoria	Australia	3128
64	Medical and Cognitive Research Unit, Austin Health Heidelberg Repatriation Hospital	Heidelberg West	Victoria	Australia	3081
65	McCusker Alzheimer's Research Foundation Inc	Nedlands	Western Australia	Australia	6009
66	Neurodegenerative Disorders Research Pty Ltd	Subiaco	Western Australia	Australia	6008
67	University Hospital Ghent Department of Neurology	Ghent		Belgium	9000
68	Jessa Hospital	Hasselt		Belgium	3500
69	GZA Sint-Augustinus	Wilrijk		Belgium	2610
70	Heritage Medical Research Clinic	Calgary	Alberta	Canada	T2N 4Z6
71	Okanagan Clinical Trials	Kelowna	British Columbia	Canada	V1Y 1Z9
72	University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders	Vancouver	British Columbia	Canada	V6T 1Z3
73	Vancouver Island Health Authority	Victoria	British Columbia	Canada	V8R 1J8
74	True North Clinical Research Halifax Inc	Halifax	Nova Scotia	Canada	B3S 1M7
75	True North Clinical Research Kentville Inc	Kentville	Nova Scotia	Canada	B4N 4K9
76	Geriatric Clinical Trials Group, St. Joseph's Health Care, Parkwood Hospital Site	London	Ontario	Canada	N6C 0A7
77	Toronto Memory Program	Toronto	Ontario	Canada	M3B 2S7
78	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
79	McGill Centre for Studies in Aging, Alzheimer Disease Research Unit	Verdun	Quebec	Canada	H4H 1R3
80	University Hospital Centre Zagreb, Department of Neurology	Zagreb		Croatia	10000
81	University Psychiatric Hospital Vrapče	Zagreb		Croatia	10090
82	University of Eastern Finland, Brain Research Unit Mediteknia	Kuopio		Finland	70210
83	Clinical Research Services Turku (CRST)	Turku		Finland	20520
84	Hôpitaux Civils de Colmar	Colmar	Cedex	France	68024
85	Centre de Recherche Clinique	Toulouse		France	31059
86	Hôpital de Charpennes	Villeurbanne		France	69100
87	Charité, University Medicine Berlin, CBF, Neurology	Berlin		Germany	12200
88	Arzeneimittelforschung Leipzig GmbH	Leipzig		Germany	04107
89	Dong-A University Hospital	Busan		Korea, Republic of	602-715
90	Gachon University Gil Medical Center	Incheon		Korea, Republic of	405-760
91	Samsung Medical Center	Seoul		Korea, Republic of	135-710
92	Seoul National University Boramae Medical Center	Seoul		Korea, Republic of	156-707
93	Seoul National University Hospital	Seoul		Korea, Republic of
94	University Kuala Lumpur Royal College of Medicine	Ipoh		Malaysia	30450
95	Hospital Sultan Ismail	Johor Bahru		Malaysia	81100
96	University Malaya Medical Centre	Kuala Lumpur		Malaysia	50603
97	Erasmus University Medical Center	Rotterdam		Netherlands	3015
98	Psychiatry Hospital "Dr. Gheorghe Preda", Department of Psychiatry III	Sibiu		Romania	550082
99	State Budgetary Healthcare Institution of Sverdlovsk region "Sverdlovsk Regional Clinical Psychiatric Hospital"	Ekaterinburg		Russian Federation	620030
100	Non-governmental Healthcare Institution "Central Clinical Hospital #6 of the JSC "Russian Railways"	Moscow		Russian Federation	109388
101	Mental Health Research Center of the Russian Academy of Medical Sciences, Gerontopsychiatry department	Moscow		Russian Federation	115522
102	Mental Health Research Center of the Russian Academy of Medical Sciences	Moscow		Russian Federation	115522
103	City Clinical Hospital #34, City Scientific Practical Neurological Center	Novosibirsk		Russian Federation	630054
104	City Geriatric Medical and Social Center	Saint Petersburg		Russian Federation	190103
105	Saint Petersburg Psychoneurological Research Institute n. a. V.M. Bekhterev	Saint Petersburg		Russian Federation	192019
106	National University Hospital (NUH)	Singapore		Singapore	119228
107	National Neuroscience Institute (NNI)	Singapore		Singapore	308433
108	Fundació ACE	Barcelona		Spain	08028
109	Hospital Clinico San Carlos	Madrid		Spain	28040
110	Hospital Universitario La Paz	Madrid		Spain	28046
111	Hospital Viamed Montecanal	Zaragoza		Spain	50006
112	Chang Gung Memorial Hospital, Kaohsiung	Kaohsiung		Taiwan
113	China Medical University Hospital	Taichung		Taiwan
114	National Taiwan University Hospital	Taipei		Taiwan
115	Taipei Veterans General Hospital	Taipei		Taiwan
116	Chang Gung Memorial Hospital, Linkou	Taoyuan		Taiwan
117	Grampian NHS, Royal Cornhill Hospital	Aberdeen		United Kingdom	AB25 2ZH
118	RICE - The Research Institute for the Care of Older People	Bath		United Kingdom	BA1 3NG
119	Belfast Health and Social Care Trust (BHSCT)	Belfast		United Kingdom	BT12 6BA
120	The Barberry Centre	Birmingham		United Kingdom	B15 2SG
121	MAC Clinical Research Ltd	Blackpool		United Kingdom	FY2 0JH
122	MAC Clinical Research Ltd	Cannock		United Kingdom	WS11 0BN
123	Sussex Partnership NHS Foundation Trust, Cognitive Treatment and Research Unit	Crowborough		United Kingdom	TN6 1HB
124	St Margaret's Hospital Mental Health Unit	Epping		United Kingdom	CM16 6TN
125	Cognition Health Ltd	Guildford		United Kingdom	GU27YD
126	MAC Clinical Research Ltd	Leeds		United Kingdom	LS10 1DU
127	Cognition Health Ltd.	London		United Kingdom	W1G 9JF
128	Imperial College Healthcare NHS Trust - Charing Cross Hospital	London		United Kingdom	W6 8RF
129	Leonard Wolfson Experimental Neurology Centre	London		United Kingdom	WC1N 3BG
130	MAC Clinical Research Ltd	Manchester		United Kingdom	M13 9NQ
131	Nuffield Department of Clinical Neurosciences	Oxford		United Kingdom	OX3 9DU
132	Redwoods Centre	Shrewsbury		United Kingdom	SY3 8DS
133	Wessex Neurological Centre, Southampton General Hospital	Southampton		United Kingdom	SO16 6YD
134	Memory Assessment and Research Centre (MARC)	Southampton		United Kingdom	SO30 3JB
135	Kingshill Research Centre, Victoria Hospital	Swindon		United Kingdom	SN3 6BW

Sponsors and Collaborators

• TauRx Therapeutics Ltd

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Mar 24, 2016
• Statistical Analysis Plan - Mar 30, 2017

More Information

Publications

None provided.

• Responsible Party: TauRx Therapeutics Ltd
• ClinicalTrials.gov Identifier: NCT02245568
• Other Study ID Numbers: TRx-237-020
• First Posted: Sep 19, 2014
• Last Update Posted: Jun 2, 2020
• Last Verified: May 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by TauRx Therapeutics Ltd: Dementia; Alzheimer Disease; bvFTD; Frontotemporal Dementia; Neurodegenerative Diseases; Brain Diseases; Cognitive Disorders
• Additional relevant MeSH terms: Alzheimer Disease; Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain

Study Results

Participant Flow

Pre-assignment Detail	Subjects who completed a Phase 2 or 3 study of LMTM were eligible to enroll, pending their ability to meet the inclusion/exclusion criteria. A total of 913 subjects enrolled; however, data for 16 subjects in Spain were later excluded (GCP issues) and 1 UK subject was never dosed. Thus, 896 subjects are included in all analyses except disposition.

Arm/Group Title	LMTM 100-300 mg/Day
Arm/Group Description	The initial LMTM dose was 200 mg/day (one 100-mg tablet twice daily), except in subjects with bvFTD who were taking a reduced dose (i.e., 100 mg/day) upon entering this extension study. The dose could be increased (after at least 13 weeks of treatment) or decreased (at any time at or after 2 weeks of treatment) by the Investigator in 100-mg increments or decrements. The maximum allowable dose was 300 mg/day (or in those countries where limited by a Competent Authority or Ethics Committee, 200 mg/day).
Period Title: Overall Study
STARTED	913
COMPLETED	60
NOT COMPLETED	853

Baseline Characteristics

Arm/Group Title	LMTM 100-300 mg/Day
Arm/Group Description	The initial LMTM dose was 200 mg/day (one 100-mg tablet twice daily), except in subjects with bvFTD who were taking a reduced dose (i.e., 100 mg/day) upon entering this extension study. The dose could be increased (after at least 13 weeks of treatment) or decreased (at any time at or after 2 weeks of treatment) by the Investigator in 100-mg increments or decrements. The maximum allowable dose was 300 mg/day (or in those countries where limited by a Competent Authority or Ethics Committee, 200 mg/day).
Overall Participants	896
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	69.2
Sex: Female, Male (Count of Participants)
Female	478 53.3%
Male	418 46.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	24 2.7%
Not Hispanic or Latino	864 96.4%
Unknown or Not Reported	8 0.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	6 0.7%
Asian	72 8%
Native Hawaiian or Other Pacific Islander	1 0.1%
Black or African American	18 2%
White	783 87.4%
More than one race	2 0.2%
Unknown or Not Reported	14 1.6%
Region of Enrollment (participants) [Number]
Singapore	22 2.5%
United States	459 51.2%
United Kingdom	161 18%
Malaysia	8 0.9%
Russia	35 3.9%
Spain	23 2.6%
Canada	51 5.7%
South Korea	13 1.5%
Netherlands	2 0.2%
Belgium	12 1.3%
Finland	18 2%
Taiwan	16 1.8%
Australia	41 4.6%
France	11 1.2%
Germany	12 1.3%
Croatia	11 1.2%
Romania	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Serious or Non-serious Adverse Events
Description	Study-emergent adverse events (including the onset of new adverse events or worsening of pre-existing adverse events) were recorded from the time of first dose in this study to the end of study participation. All laboratory test, vital sign, or electrocardiogram parameter abnormalities deemed clinically significant by the Investigator were to be reported as adverse events.
Time Frame	Up to 34 months

Outcome Measure Data

Analysis Population Description

The safety population was composed of participants dosed with 100-300 mg LMTM who were used for analysis. Safety was assessed over time by means of adverse event and concomitant medication recording; clinical laboratory tests; vital sign measurements and weight; 12-lead electrocardiograms; and targeted physical and neurological examinations.

Arm/Group Title	LMTM 100-300 mg/Day
Arm/Group Description	The initial LMTM dose was 200 mg/day (one 100-mg tablet twice daily), except in subjects with bvFTD who were taking a reduced dose (i.e., 100 mg/day) upon entering this extension study. The dose could be increased (after at least 13 weeks of treatment) or decreased (at any time at or after 2 weeks of treatment) by the Investigator in 100-mg increments or decrements. The maximum allowable dose was 300 mg/day (or in those countries where limited by a Competent Authority or Ethics Committee, 200 mg/day).
Measure Participants	896
Count of Participants [Participants]	734 81.9%

Adverse Events

Time Frame	Up to 34 months
Adverse Event Reporting Description	Study-emergent adverse events (including the onset of new adverse events or worsening of pre-existing adverse events) were recorded from the time of first dose in this study to the end of study participation. All laboratory test, vital sign, or electrocardiogram parameter abnormalities deemed clinically significant by the Investigator were to be reported as adverse events.
Arm/Group Title	LMTM 100-300 mg/Day
Arm/Group Description	The initial LMTM dose was 200 mg/day (one 100-mg tablet twice daily), except in subjects with bvFTD who were taking a reduced dose (i.e., 100 mg/day) upon entering this extension study. The dose could be increased (after at least 13 weeks of treatment) or decreased (at any time at or after 2 weeks of treatment) by the Investigator in 100-mg increments or decrements. The maximum allowable dose was 300 mg/day (or in those countries where limited by a Competent Authority or Ethics Committee, 200 mg/day).
All Cause Mortality
	LMTM 100-300 mg/Day
	Affected / at Risk (%)	# Events
Total	15/896 (1.7%)
Serious Adverse Events
	LMTM 100-300 mg/Day
	Affected / at Risk (%)	# Events
Total	146/896 (16.3%)
Blood and lymphatic system disorders
Anaemia	1/896 (0.1%)	1
Haemolytic anaemia	2/896 (0.2%)	2
Neutropenia	1/896 (0.1%)	1
Thrombocytopenia	1/896 (0.1%)	1
Cardiac disorders
Acute coronary syndrome	1/896 (0.1%)	1
Acute myocardial infarction	1/896 (0.1%)	1
Atrial fibrillation	1/896 (0.1%)	1
Atrial flutter	2/896 (0.2%)	2
Atrioventricular block	1/896 (0.1%)	1
Bradycardia	2/896 (0.2%)	3
Cardiac arrest	1/896 (0.1%)	1
Cardiac failure congestive	2/896 (0.2%)	2
Cardio-respiratory arrest	1/896 (0.1%)	1
Myocardial infarction	1/896 (0.1%)	1
Pericardial effusion	1/896 (0.1%)	1
Sick sinus syndrome	1/896 (0.1%)	1
Congenital, familial and genetic disorders
Hydrocele	1/896 (0.1%)	1
Gastrointestinal disorders
Abdominal pain	1/896 (0.1%)	1
Colitis microscopic	2/896 (0.2%)	2
Diarrhoea	1/896 (0.1%)	1
Duodenal ulcer perforation	1/896 (0.1%)	1
Faecaloma	1/896 (0.1%)	1
Gastritis	1/896 (0.1%)	1
Intestinal obstruction	1/896 (0.1%)	1
Large intestinal obstruction	1/896 (0.1%)	1
Nausea	1/896 (0.1%)	1
Pancreatitis	1/896 (0.1%)	1
Vomiting	1/896 (0.1%)	1
General disorders
Chest pain	4/896 (0.4%)	4
Hepatobiliary disorders
Cholecystitis	1/896 (0.1%)	1
Cholelithiasis	2/896 (0.2%)	2
Immune system disorders
Hypersensitivity	1/896 (0.1%)	1
Infections and infestations
Appendicitis	3/896 (0.3%)	3
Bacterial pyelonephritis	1/896 (0.1%)	1
Bronchitis	1/896 (0.1%)	1
Cellulitis	1/896 (0.1%)	1
Cholecystitis infective	1/896 (0.1%)	1
Clostridium difficile infection	1/896 (0.1%)	1
Lower respiratory tract infection	1/896 (0.1%)	1
Pneumonia	6/896 (0.7%)	6
Sepsis	4/896 (0.4%)	5
Urinary tract infection	11/896 (1.2%)	11
Urosepsis	1/896 (0.1%)	1
Viral upper respiratory tract infection	1/896 (0.1%)	1
Injury, poisoning and procedural complications
Concussion	1/896 (0.1%)	1
Facial bones fracture	1/896 (0.1%)	1
Fall	9/896 (1%)	9
Femoral neck fracture	1/896 (0.1%)	1
Femur fracture	2/896 (0.2%)	2
Hip fracture	2/896 (0.2%)	2
Humerus fracture	1/896 (0.1%)	1
Overdose	1/896 (0.1%)	1
Pelvic fracture	1/896 (0.1%)	1
Pulmonary contusion	1/896 (0.1%)	1
Rib fracture	1/896 (0.1%)	1
Road traffic accident	1/896 (0.1%)	1
Spinal compression fracture	1/896 (0.1%)	1
Subdural haematoma	1/896 (0.1%)	1
Upper limb fracture	1/896 (0.1%)	1
Investigations
Blood glucose increased	1/896 (0.1%)	1
Liver function test abnormal	1/896 (0.1%)	1
Weight decreased	1/896 (0.1%)	1
Metabolism and nutrition disorders
Dehydration	4/896 (0.4%)	4
Diabetic ketoacidosis	1/896 (0.1%)	1
Hypercalcaemia	1/896 (0.1%)	1
Hypokalaemia	1/896 (0.1%)	1
Hypovolaemia	1/896 (0.1%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/896 (0.1%)	1
Costochondritis	1/896 (0.1%)	1
Musculoskeletal pain	1/896 (0.1%)	1
Rotator cuff syndrome	2/896 (0.2%)	2
Spondylolisthesis	1/896 (0.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma	1/896 (0.1%)	1
Bladder cancer	1/896 (0.1%)	1
Breast cancer	1/896 (0.1%)	1
Breast cancer recurrent	1/896 (0.1%)	1
Chronic lymphocytic leukaemia	1/896 (0.1%)	1
Malignant melanoma	1/896 (0.1%)	1
Metastatic neoplasm	1/896 (0.1%)	1
Non-Hodgkin's lymphoma	1/896 (0.1%)	1
Oesophageal carcinoma	1/896 (0.1%)	1
Ovarian cancer	1/896 (0.1%)	1
Pancreatic carcinoma	1/896 (0.1%)	1
Prostate cancer	1/896 (0.1%)	1
Renal cell carcinoma	1/896 (0.1%)	1
Squamous cell carcinoma of lung	1/896 (0.1%)	1
Tonsil cancer	1/896 (0.1%)	1
Nervous system disorders
Altered state of consciousness	1/896 (0.1%)	1
Cerebral haemorrhage	1/896 (0.1%)	1
Cerebrovascular accident	2/896 (0.2%)	2
Coordination abnormal	1/896 (0.1%)	1
Dementia	1/896 (0.1%)	1
Dementia Alzheimer's type	3/896 (0.3%)	3
Grand mal convlusion	1/896 (0.1%)	1
Headache	1/896 (0.1%)	1
Ischaemic stroke	1/896 (0.1%)	1
Lacunar infarction	1/896 (0.1%)	1
Loss of consciousness	2/896 (0.2%)	2
Migraine	1/896 (0.1%)	1
Presyncope	1/896 (0.1%)	1
Seizure like phenomena	1/896 (0.1%)	1
Serotonin syndrome	1/896 (0.1%)	1
Syncope	6/896 (0.7%)	7
Transient ischaemic attack	4/896 (0.4%)	4
Tremor	1/896 (0.1%)	1
VIIth nerve paralysis	1/896 (0.1%)	1
Psychiatric disorders
Abnormal behavior	1/896 (0.1%)	1
Aggression	3/896 (0.3%)	3
Agitation	4/896 (0.4%)	4
Confusional state	1/896 (0.1%)	1
Delirium	3/896 (0.3%)	3
Hallucination, visual	1/896 (0.1%)	1
Hypersexuality	1/896 (0.1%)	1
Mental status changes	3/896 (0.3%)	4
Staring	1/896 (0.1%)	1
Suicidal ideation	3/896 (0.3%)	3
Suicidal attempt	1/896 (0.1%)	1
Renal and urinary disorders
Bladder mass	1/896 (0.1%)	1
Bladder prolapse	1/896 (0.1%)	1
Cystitis noninfective	1/896 (0.1%)	1
Haematuria	1/896 (0.1%)	1
Nephrolithiasis	2/896 (0.2%)	2
Nephropathy	1/896 (0.1%)	1
Renal failure, acute	2/896 (0.2%)	2
Renal impairment	1/896 (0.1%)	1
Urinary tract obstruction	1/896 (0.1%)	1
Reproductive system and breast disorders
Uterine prolapse	2/896 (0.2%)	2
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/896 (0.1%)	1
Acute respiratory failure	4/896 (0.4%)	4
Dyspnoea	1/896 (0.1%)	1
Hypoxia	1/896 (0.1%)	1
Pleural effusion	1/896 (0.1%)	2
Pulmonary embolism	3/896 (0.3%)	3
Respiratory failure	1/896 (0.1%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/896 (0.1%)	1
Vascular disorders
Circulatory collapse	2/896 (0.2%)	3
Deep vein thrombosis	1/896 (0.1%)	1
Hypertensive crisis	1/896 (0.1%)	1
Hypotension	1/896 (0.1%)	1
Orthostatic hypotension	2/896 (0.2%)	2
Thrombosis	1/896 (0.1%)	1
Other (Not Including Serious) Adverse Events
	LMTM 100-300 mg/Day
	Affected / at Risk (%)	# Events
Total	717/896 (80%)
Blood and lymphatic system disorders
Anaemia	43/896 (4.8%)	45
Gastrointestinal disorders
Diarrhoea	123/896 (13.7%)	174
Nausea	44/896 (4.9%)	56
Constipation	18/896 (2%)	19
Vomiting	36/896 (4%)	40
General disorders
Fatigue	20/896 (2.2%)	23
Infections and infestations
Urinary tract infection	49/896 (5.5%)	72
Lower respiratory tract infection	18/896 (2%)	21
Nasopharyngitis	27/896 (3%)	31
Upper respiratory tract infection	27/896 (3%)	34
Injury, poisoning and procedural complications
Fall	62/896 (6.9%)	79
Investigations
Blood creatine phosphokinase increased	21/896 (2.3%)	21
Creatinine renal clearance decreased	33/896 (3.7%)	37
Haemoglobin decreased	40/896 (4.5%)	44
Weight decreased	30/896 (3.3%)	31
Musculoskeletal and connective tissue disorders
Arthralgia	27/896 (3%)	34
Back pain	18/896 (2%)	21
Nervous system disorders
Dizziness	23/896 (2.6%)	31
Headache	29/896 (3.2%)	33
Psychiatric disorders
Agitation	46/896 (5.1%)	59
Anxiety	32/896 (3.6%)	35
Confusional state	34/896 (3.8%)	39
Depression	21/896 (2.3%)	21
Insomnia	19/896 (2.1%)	21
Renal and urinary disorders
Pollakiuria	55/896 (6.1%)	58
Urinary incontinence	60/896 (6.7%)	67
Dysuria	39/896 (4.4%)	45
Micturition urgency	29/896 (3.2%)	30
Respiratory, thoracic and mediastinal disorders
Cough	24/896 (2.7%)	24
Vascular disorders
Hypertension	20/896 (2.2%)	20

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.