Safety and Efficacy Study of Ladostigil in Mild to Moderate Probable Alzheimer's Disease

• Sponsor: Avraham Pharmaceuticals Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01354691
• Collaborator: (none)
• Enrollment: 200
• Locations: 19
• Arms: 2
• Duration (Months): 24.9
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

For many, Alzheimer's disease is the number one medical issue facing our aging society. It is a late onset neurodegenerative disease, frequently under diagnosed, that impairs memory and cognitive performance. There are no known treatments that can either prevent or reverse its progression. Consequently, there still remains a need to evaluate treatments which can better stabilize the symptoms of this disease. These symptoms frequently include decreased functional capacity and negative psychological attributes (e,g, depression, anxiety) in association with the memory and cognition deficits. This current study is being done to assess an investigational compound that has been designed to not only improved the cognitive status of affected patients but to also better manage all symptoms. Hence, the ultimate goal is to provide patients with an improved quality of life by slowing the progression of this neurodegenerative disease

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease; Dementia; Memory Loss; Cognitive Impairment	Drug: ladostigil hemitartrate	Phase 2

Detailed Description

This is a phase II, proof of concept study to evaluate the safety and efficacy of the investigational compound ladostigil versus placebo in mild to moderate Alzheimer's disease patients. The randomized, double-blind, placebo-controlled phase of the trial will be 26 weeks in duration and will involve two cohorts (i.e. one arm receiving ladostigil and one arm receiving placebo). After the initial 26 week period, all participating subjects will receive 26 weeks of treatment with ladostigil (i.e. the open label phase). A total of five territories will be participating in this trial. These include Austria, Croatia, Germany, Serbia and Spain.

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 6-Month Prospective, Multi-Center, Double-Blind, Placebo-Controlled, Randomized, Adaptive-Trial-Design Study to Evaluate the Safety and Efficacy of 80mg b.i.d Ladostigil in Patients With Mild to Moderate Probable Alzheimer's Disease
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ladostigil hemitartrate Ladostigil capsules 80 mg	Drug: ladostigil hemitartrate; Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.
Placebo Comparator: Placebo Placebo capsules	Drug: ladostigil hemitartrate; Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.

Outcome Measures

Primary Outcome Measures

1. ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale [26 weeks]

   Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia, The ADAS-Cog consist of 11 questions: Word Recall Task Naming Objects and Fingers Following Commands Constructional Praxis Ideational Praxis Orientation Word Recognition Task Remembering Test Directions Spoken Language Comprehension Word-Finding Difficulty Item scores are summed. Low total scores indicate better cognitive performance. Minimum score 0 is best and maximum is 70 - worst. For the purposes of analyses the change from baseline is computed to each administration of the test.

Secondary Outcome Measures

1. Neuropsychiatric Inventory (NPI) [52 weeks]

   The Neuropsychiatric Inventory (NPI) was developed to assess psychopathology in dementia patients. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities. The severity and frequency of each neuropsychiatric symptom are rated on the basis of scripted questions administered to the patient's caregiver. Higher the score the more disturbed, lower score is thus better. Minimum score is 0 and maximum is 80.

2. Cornell Scale for Depression in Dementia (CSDD) [52 weeks]

   The Cornell Scale for Depression in Dementia (CSDD) was developed specifically to assess signs and symptoms of major depression in dementia on the basis of a semi-structured interview of a qualified informant. The CSDD evaluates a broad spectrum of depressive signs and synptoms and includes items from other depression scales. Information is obtained from interview of the caregiver as well as from direct observation and interview of the patient CSDD is a 19 item scale assessing depressive status. Higher score more depression. The scale ranges from 0-no depression to 38 maximum depression.

3. Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) [52 weeks]

   The Activities of Daily Living ADCS-ADL is a caregiver-based ADL scale composed of 23 items developed for use in dementia clinical trials. It is designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests as well as making judgments and decisions. For each ADL, the caregiver is asked whether the patient attempted the activity during the past four weeks. If the answer is positive, the caregiver is then asked to choose the single most accurate definition of the patient's level of performance. Assessment of functional activity status is a 23 item scale measuring impairment in functioning. The scale total score ranges from 0-profound impairment to 30 normal functioning (no impairments)

4. Mini-Mental State Examination [52 weeks]

   The MMSE is a frequently used screening instrument for AD drug studies. The instrument provides for evaluation of orientation, memory, attention, concentration, naming, repetition, comprehension, ability to create a sentence and to copy two intersecting polygons. This examination is frequently used by physicians in the original diagnosis of AD, and in its subsequent progression, because it can be easily performed in the routine care of patients. A lower score indicates more cognitive impairment. The highest (best) score is 30. The Mini-Mental State Examination, MMSE, is a 30-point questionnaire measures cognitive impairment to screen for dementia. Items are totaled. The scale ranges from 0-most impairment to 30 (normal) no impairment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• AD diagnosis according to NINCDS-ADRDA criteria

• Mild to moderate AD according to MMSE 14-24 inclusive

• MRI or CT assessment within 6 months before baseline, corroborating the clinical diagnosis and excluding other potential causes of dementia especially cerebrovascular lesions

• Absence of major depressive disease according to CSDD of less than or equal to 18

• Modified Hachinski Ischemic Scale equal to or below 4

• Education for eight or more years

• Previous decline in cognition for more than six months as documented in patient medical records

• A caregiver available and living in the same household or interacting with the patient daily and available if necessary to assure administration of investigational product

• Patients living at home or nursing home setting without continuous nursing care

• General health status acceptable for participation in a 12-month clinical trial and ability to swallow oral medication

• No history of treatment with rivastigmine

• For patients with either donepezil or galantamine anti-cholinesterase inhibitor treatment prescribed, stopped treatment four weeks prior to screening

• For patients with memantine treatment prescribed, stopped treatment four weeks prior to screening

Exclusion Criteria:

• Other primary degenerative dementias (e.g. dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Jacob-Creutzfeldt disease)

• Other neurodegenerative conditions (Parkinson's disease. amyotrophic lateral sclerosis, etc)

• Other central nervous system diseases (severe head trauma, tumors, subdural hematoma, etc)

• A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder

• Seizure disorders

• Other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc)

• Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations

• Other unstable, chronic or clinically significant medical conditions involving major organs like kidney, liver, lungs and heart/vasculature

• Hospitalization or change of chronic concomitant medications one month prior to screening or during screening period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Univeritat Graz, Universitatsklinik fur Neurologie, Auenbruggerplatz 22	Graz		Austria	8036
2	Privatordination Horn, HamerlingstraBe 15	Horn		Austria	3580
3	Allgemeines Krankenhaus der Stadt Linz, KrankenhausstraBe 9	Linz		Austria	4020
4	Privatordination, Lainzerstrasse 20	Wein		Austria	1130
5	General Hospital Pula, Negrijeva 6	Pula		Croatia	52100
6	General Hospital Zabok, Bracak 8	Zabok		Croatia	49210
7	Clinical Hospital Center Zagreb, Kispaticeva 12	Zagreb		Croatia	10000
8	Clinical Hospital Dubrava, Avenija Gojka Suska 6	Zagreb		Croatia	10000
9	Polyclinic Neuron, Salata 12	Zagreb		Croatia	10000
10	Psychiatric Hospital Vrapce, Bolnicka cesta 32	Zagreb		Croatia	10090
11	Klinische Forschung Hamburg GmbH, Hoheluftaussee 18	Hamburg		Germany	20253
12	Klinische Forschung Schwerin GmbH, FriedrichstraBe 1	Schwerin		Germany	19055
13	Studienzentrum Nordwest, Lange StraBe 23-25	Westerstede		Germany	26655
14	Military Medical Academy, Crnotravska 17	Belgrade		Serbia	11000
15	Clinical Centre of Serbia, Dr. Subotica 6	Belgrad		Serbia	11000
16	CAE Oroitu Centro Atencion Especializada C/Jata, 9	Algorta		Spain	48993
17	Centro Geroinnova Barcelona, Calle Mandoni n 17	Barcelona		Spain	08004
18	Fundacio ACE, Institut Catala de Neurosciencies Aplicadas, C/Margues de Sentmenat 35-37	Barcelona		Spain	08014
19	Institud d' Assistencia Sanitaria de Girona, Edifici La Republica - C/Dr. Castany, s/n	Salt		Spain	17190

Sponsors and Collaborators

• Avraham Pharmaceuticals Ltd

Investigators

• Principal Investigator: Reinhold Schmidt, MD, MEDIZINISCHE UNIVERSITAT GRAZ

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Avraham Pharmaceuticals Ltd
• ClinicalTrials.gov Identifier: NCT01354691
• Other Study ID Numbers: CR100101/CO15570
• First Posted: May 17, 2011
• Last Update Posted: Jul 30, 2020
• Last Verified: Jul 1, 2018

• Keywords provided by Avraham Pharmaceuticals Ltd: Alzheimer's Disease; Dementia; Memory Loss; Cognitive Impairment; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Delirium, Dementia, Amnestic, Cognitive Disorders; Mental Disorders; Depression; Anxiety
• Additional relevant MeSH terms: Alzheimer Disease; Dementia; Memory Disorders; Amnesia; Cognitive Dysfunction

Study Results

Participant Flow

Arm/Group Title	Ladostigil Hemitartrate	Placebo
Arm/Group Description	Ladostigil capsules 80 mg ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.	Placebo capsules ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.
Period Title: Overall Study
STARTED	101	99
ITT	99	96
PP	79	75
COMPLETED	80	77
NOT COMPLETED	21	22

Baseline Characteristics

Arm/Group Title	Ladostigil Hemitartrate	Placebo	Total
Arm/Group Description	Ladostigil capsules 80 mg ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.	Placebo capsules ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.	Total of all reporting groups
Overall Participants	101	99	200
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	15 14.9%	15 15.2%	30 15%
>=65 years	86 85.1%	84 84.8%	170 85%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	74.25 (6.73)	74.28 (6.92)	74.26 (6.8)
Sex: Female, Male (Count of Participants)
Female	56 55.4%	60 60.6%	116 58%
Male	45 44.6%	39 39.4%	84 42%
Race/Ethnicity, Customized (Count of Participants)
White or Caucasian	101 100%	99 100%	200 100%
Other	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Austria	28 27.7%	27 27.3%	55 27.5%
Serbia	4 4%	2 2%	6 3%
Germany	9 8.9%	8 8.1%	17 8.5%
Croatia	44 43.6%	45 45.5%	89 44.5%
Spain	16 15.8%	17 17.2%	33 16.5%

Outcome Measures

1. Primary Outcome

Title	ADAS-Cog: Alzheimer's Disease Assessment Scale-Cognitive Subscale
Description	Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) is a brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia, The ADAS-Cog consist of 11 questions: Word Recall Task Naming Objects and Fingers Following Commands Constructional Praxis Ideational Praxis Orientation Word Recognition Task Remembering Test Directions Spoken Language Comprehension Word-Finding Difficulty Item scores are summed. Low total scores indicate better cognitive performance. Minimum score 0 is best and maximum is 70 - worst. For the purposes of analyses the change from baseline is computed to each administration of the test.
Time Frame	26 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ladostigil Hemitartrate	Placebo
Arm/Group Description	Ladostigil capsules 80 mg ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.	Placebo capsules ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.
Measure Participants	99	96
Mean (Standard Deviation) [score on scale - baseline to endpoint]	-.27 (5.41)	0.19 (5.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ladostigil Hemitartrate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.67
	Comments
	Method	ANCOVA
	Comments

2. Secondary Outcome

Title	Neuropsychiatric Inventory (NPI)
Description	The Neuropsychiatric Inventory (NPI) was developed to assess psychopathology in dementia patients. It evaluates 12 neuropsychiatric disturbances common in dementia: delusions, hallucinations, agitation, dysphoria, anxiety, apathy, irritability, euphoria, disinhibition, aberrant motor behavior, night-time behavior disturbances, and appetite and eating abnormalities. The severity and frequency of each neuropsychiatric symptom are rated on the basis of scripted questions administered to the patient's caregiver. Higher the score the more disturbed, lower score is thus better. Minimum score is 0 and maximum is 80.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ladostigil Hemitartrate	Placebo
Arm/Group Description	Ladostigil capsules 80 mg ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.	Placebo capsules ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.
Measure Participants	99	96
Mean (Standard Deviation) [score on scale - baseline to endpoint]	2.51 (11.27)	0.66 (7.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ladostigil Hemitartrate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.21
	Comments
	Method	ANCOVA
	Comments

3. Secondary Outcome

Title	Cornell Scale for Depression in Dementia (CSDD)
Description	The Cornell Scale for Depression in Dementia (CSDD) was developed specifically to assess signs and symptoms of major depression in dementia on the basis of a semi-structured interview of a qualified informant. The CSDD evaluates a broad spectrum of depressive signs and synptoms and includes items from other depression scales. Information is obtained from interview of the caregiver as well as from direct observation and interview of the patient CSDD is a 19 item scale assessing depressive status. Higher score more depression. The scale ranges from 0-no depression to 38 maximum depression.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ladostigil Hemitartrate	Placebo
Arm/Group Description	Ladostigil capsules 80 mg ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.	Placebo capsules ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.
Measure Participants	93	86
Mean (Standard Deviation) [score on scale - baseline to endpoint]	-0.08 (2.81)	-0.45 (3.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ladostigil Hemitartrate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.78
	Comments
	Method	ANCOVA
	Comments

4. Secondary Outcome

Title	Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Description	The Activities of Daily Living ADCS-ADL is a caregiver-based ADL scale composed of 23 items developed for use in dementia clinical trials. It is designed to assess the patient's performance of both basic and instrumental activities of daily living such as those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests as well as making judgments and decisions. For each ADL, the caregiver is asked whether the patient attempted the activity during the past four weeks. If the answer is positive, the caregiver is then asked to choose the single most accurate definition of the patient's level of performance. Assessment of functional activity status is a 23 item scale measuring impairment in functioning. The scale total score ranges from 0-profound impairment to 30 normal functioning (no impairments)
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ladostigil Hemitartrate	Placebo
Arm/Group Description	Ladostigil capsules 80 mg ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.	Placebo capsules ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.
Measure Participants	99	96
Mean (Standard Deviation) [score on scale - baseline to endpoint]	-1.88 (9.54)	-1.57 (7.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ladostigil Hemitartrate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.83
	Comments
	Method	ANCOVA
	Comments

5. Secondary Outcome

Title	Mini-Mental State Examination
Description	The MMSE is a frequently used screening instrument for AD drug studies. The instrument provides for evaluation of orientation, memory, attention, concentration, naming, repetition, comprehension, ability to create a sentence and to copy two intersecting polygons. This examination is frequently used by physicians in the original diagnosis of AD, and in its subsequent progression, because it can be easily performed in the routine care of patients. A lower score indicates more cognitive impairment. The highest (best) score is 30. The Mini-Mental State Examination, MMSE, is a 30-point questionnaire measures cognitive impairment to screen for dementia. Items are totaled. The scale ranges from 0-most impairment to 30 (normal) no impairment.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ladostigil Hemitartrate	Placebo
Arm/Group Description	Ladostigil capsules 80 mg ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.	Placebo capsules ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.
Measure Participants	99	96
Mean (Standard Deviation) [change in score - baseline to endpoint]	0.80 (2.73)	0.60 (2.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ladostigil Hemitartrate, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=.77
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	26 weeks
Adverse Event Reporting Description	Enrolled patients Ladostigil 101(100.0%) Placebo 99(100.0%) ITT Population Ladostigil 99(98.02%) Placebo 96(96.97%) PP Population Ladostigil 79(78.22%) Placebo 75(75.76%) Safety Population Ladostigil 100(99.01%) Placebo 98(98.99%) one patient discontinued the study in each group before administration of drug that is why the Safety Population is: Ladostigil 100(99.01%) Placebo 98(98.99%)
Arm/Group Title	Ladostigil Hemitartrate		Placebo
Arm/Group Description	Ladostigil capsules 80 mg ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.		Placebo capsules ladostigil hemitartrate: Final dosage strength of 80mg b.i.d will begin at Day 22 following a 21 day dose escalation phase involving 40mg and 60mg b.i.d dosage strengths. Oral, solid dosage.
All Cause Mortality
	Ladostigil Hemitartrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/100 (0%)		2/98 (2%)
Serious Adverse Events
	Ladostigil Hemitartrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/100 (7%)		7/98 (7.1%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCT	1/100 (1%)	1	0/98 (0%)	0
Gastrointestinal disorders
Acute Cholecystitis	0/100 (0%)	0	1/98 (1%)	1
Obstipation	0/100 (0%)	0	1/98 (1%)	1
Infections and infestations
Urinary Infection	0/100 (0%)	0	2/98 (2%)	2
Injury, poisoning and procedural complications
Sun Stroke	1/100 (1%)	1	0/98 (0%)	0
POLYTRAUMATISM	0/100 (0%)	0	1/98 (1%)	1
Musculoskeletal and connective tissue disorders
Elbow Fracture	1/100 (1%)	1	0/98 (0%)	0
Femur fracture subtrochan	1/100 (1%)	1	0/98 (0%)	0
Arthritis left ankle	0/100 (0%)	0	1/98 (1%)	1
Respiratory, thoracic and mediastinal disorders
Sick Sinus Syndrome	1/100 (1%)	1	0/98 (0%)	0
Thoracic Pain	1/100 (1%)	1	0/98 (0%)	0
Pneunomia	0/100 (0%)	0	1/98 (1%)	1
Vascular disorders
Brain Stroke	1/100 (1%)	1	0/98 (0%)	0
Other (Not Including Serious) Adverse Events
	Ladostigil Hemitartrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/100 (11%)		2/98 (2%)
Cardiac disorders
Essential hypertension	6/100 (6%)	6	0/98 (0%)	0
Gastrointestinal disorders
Diarrhoea	6/100 (6%)	6	2/98 (2%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.