CompletedPhase 2Results posted

A 3 Year Study to Evaluate the Safety and Efficacy of Low Dose Ladostigil in Patients With Mild Cognitive Impairment

A 36-month, Multi-centre, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of Low Dose Ladostigil in Patients With Mild Cognitive Impairment (MCI)

Lead sponsor

Avraham Pharmaceuticals Ltd

Asset

ladostigil hemitartrate

Listed sites

Recruiting sites

Enrollment

210

actual

Study population

MCI / preclinical Alzheimer’s

Key I/E criteria

•Alzheimer's disease•MMSE ≥24

Primary endpoint

•Conversion From Mild Cognitive Impairment to Alzheimer's Disease

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Eudract number2011-004187-30

Org study IDCO17730

NCT IDNCT01429623

Timeline

Milestones

Study first posted2011-09-07estimated

Study start2012-02 (month precision)

Primary completion2016-07actual (month precision)

Study completion2016-09actual (month precision)

Last update posted2017-06-15actual

Results first posted2017-06-15actual

Assets

Drug assets

ladostigil hemitartrate

Study populations

Who this study enrolls

MCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age55 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Men and women (non-childbearing potential) with a diagnosis of Mild Cognitive Impairment (MCI) according to consensus criteria as defined by Petersen

•Abnormal memory function will be evaluated by Verbal Paired Associates from the Wechsler Memory Scale - Revised. Norm values for healthy adults in two age cohorts are:

a)50-70 years 19.7 (SD=2.9) and

b)75-95 years 18.3 (SD=2.8). Patients that score < or = 23 will be included.

•Clinical Dementia Rating (CDR) score of 0.5 (Memory box score 0.5 or 1, no box score > 1)

•Mini Mental State Examination (MMSE) > 24 and < or = 30

•General cognition and functional performance is sufficiently preserved such that a diagnosis of AD can be excluded by the site physician at the time of the screening visit.

•No significant cerebrovascular disease indicated by Modified Hackinski Ischaemic Score equal to or below 4

•Age 55-85 years based upon correlation of cognition and Scheltens score observed in this age range

•Geriatric Depression Scale (GDS) of < or = 5

•An informer who has frequent contact with the subject (e.g. an average of 10 hours per week or more) is available and agrees to monitor administration of study drug, to observe the subject for adverse events and to accompany the subject to clinical visits during the trial, if the presence of the informer is required.

•All patients have to undergo an MRI scan after the screening visit, i.e. during the screening visit, irrespective of MRIs having been performed prior to entry into the study. MRI findings have to be consistent with a diagnosis of MCI.

•Central rating of medial temporal lobe according to Scheltens scale. The right and left medial temporal structures will be rated separately and an overall estimate will be deduced using the average of the two ratings. An average score > 1 is required to make patients eligible for the study.

•Adequate visual and auditory acuity must be demonstrated to allow for neuropsychological testing.

•Good general health status acceptable for participation in a 36-month clinical trial, with no additional diseases expected to interfere with the study

•ECG without clinically significant abnormalities according to exclusion criteria listed below

•Subject is not pregnant, lactating or of childbearing potential (i.e. women must be two years post menopausal or surgically sterile)

•Signed informed consent by patient and informer prior to any study specific procedure

Exclusion criteria

•Failure to perform screening or baseline examinations

•Any significant neurological disease other than suspected MCI

•MRI exclusion criteria which allow for mild concomitant vascular lesions are:

-Thromboembolic infarction

-Other focal lesions which may be responsible for the cognitive status of the patient such as infectious disease, space-occupying lesions, normal pressure hydrocephalus or any other abnormalities associated with significant central nervous disease

-More than one lacunar infarct defined as a focal lesion of CSF signal intensity with a diameter of < 1.5cm in any dimension

-Any lacunar infarct in a strategically important location such as the thalamus, hippocampus of either hemisphere, head of the left caudate

-White matter lesions involving more than 25% of the hemispheric white matter

-Implants such as pacemakers, insulin pumps, cochlear implants, nerve stimulators, implantable cardioverter defibrillators, and other medical implants that have not been certified for MRI

-Ferromagnetic foreign bodies such as shell fragments need to be considered on an individual basis

-Metallic implants that can cause artifacts and RF induced heating such as surgical prostheses or aneurysm clips need to be considered on an individual basis

•Clinical or laboratory findings consistent with:

-Central nervous system diseases such as those resulting from severe head trauma, tumours, subdural haematomas or other space occupying processes, etc

-Seizure disorder

-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)

•History or evidence of schizophrenia or bipolar disorder (DSM IV criteria); active major depression

•Clinically significant advanced or unstable disease that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as:

-Malignant tumours within the last five years except skin malignancies (other than melanoma) or indolent prostate cancer

-Metastases

-History of myocardial infarction within one year prior to screening or unstable or severe cardiovascular disease including angina or congestive heart failure with symptoms at rest

-Uncontrolled hypertension (systolic pressure > 170mmHg or diastolic pressure > 100mmHg)

-Bradycardia (persistent heart beat < 50/min) or tachycardia ( persistent heart beat > 100/min)

-AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males > 450msec, females > 470msec)

-Clinically significant obstructive pulmonary disease or asthma

-Clinically significant laboratory findings that indicate abnormalities in blood biochemistry, blood haematology or urinalysis

-Uncontrolled diabetes mellitus defined by HbA1c > 8.5

-Clinically significant liver disease, coagulopathy or vitamin K deficiency within the past two years prior to screening

-Renal insufficiency (serum creatinine > mg/dl or creatinine clearance < or = to 45ml/min according to Cockgroft-Gault formula); in case of creatinine clearance < or = 45ml/min, an alternative verification of the renal function must be completed using cystatin C analysis. In case of normal level of cystatin C, the patient can be included in the study.

•Any prior use of medications approved by local authorities for the treatment of Alzheimer's disease (e.g. tacrine, donepezil, rivastigmine, galantamine, memantine or other newly approved medications)

•Disability that may prevent the subject from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc)

•Women who are fertile and of child bearing potential

•Chronic daily intake of antidepressants as noted in section 9.5 of the clinical study protocol

•Suspected or known drug or alcohol abuse, i.e. more than approximately 60g alcohol (approximately 1 lter of beer or 0.5 liter of wine) per day as indicated by elevated MCV significantly above normal value at screening

•Suspected or known allergy to any components of the study treatments

•Enrollment in another investigational study or intake of investigational drug within the previous three months

•Any condition (e.g. epilepsy) which in the opinion of the investigator makes the patient unsuitable for inclusion

Endpoints (8)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Memory

Function / daily living

Behavior / neuropsychiatric

Global cognition

2 endpoints

Primary/protocol endpoint

Conversion From Mild Cognitive Impairment to Alzheimer's Disease Compared to Placebo

Time frame:3,6,12,18,24,30 and 36 months

event count, event

Primary/registry result

Conversion From Mild Cognitive Impairment to Alzheimer's Disease Compared to Placebo

Time frame:3,6,12,18,24,30 and 36 months

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Ladostigil Hemitartraten=99 Participants	14	-
Placebo Controln=103 Participants	21	-

Odds Ratio (OR)1.5595% CI0.74 - 3.25p<0.16Log Rank

Memory

2 endpoints

Secondary/protocol endpoint

Change in Neuropsychiatric Test Battery for Ladostigil Versus Placebo Population

Time frame:3,6,12,18,24,30 and 36 months

change from baseline, improvement

Secondary/registry result

Change in Neuropsychiatric Test Battery for Ladostigil Versus Placebo Population

Time frame:3,6,12,18,24,30 and 36 months

change from baseline, improvement

Posted result

Group	Value (mean), Change from basline on units on a scale	Standard deviation
Ladostigil Hemitartraten=99 Participants	.21	.55
Placebo Controln=103 Participants	.17	.43

Mean Difference (Net)-0.066p<0.32Mixed Models Analysis

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change in Disability Assessment in Dementia for Ladostigil Versus Placebo Population

Time frame:3,6,12,18,24,30 and 36 months

change from baseline, improvement

Secondary/registry result

Change in Disability Assessment in Dementia for Ladostigil Versus Placebo Population

Time frame:3,6,12,18,24,30 and 36 months

change from baseline, improvement

Posted result

Group	Value (mean), Change from basline on units on a scale	Standard deviation
Ladostigil Hemitartraten=99 Participants	-0.77	8.43
Placebo Controln=103 Participants	-0.40	5.11

Mean Difference (Net).79p<0.97Mixed Models Analysis

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Change in Geriatric Depression Scale for Ladostigil Versus Placebo Population

Time frame:3,6,12,18,24,30 and 36 months

change from baseline, improvement

Secondary/registry result

Change in Geriatric Depression Scale for Ladostigil Versus Placebo Population

Time frame:3,6,12,18,24,30 and 36 months

change from baseline, improvement

Posted result

Group	Value (mean), Change from basline on units on a scale	Standard deviation
Ladostigil Hemitartraten=99 Participants	.084	1.70
Placebo Controln=103 Participants	.242	1.87

Mean Difference (Net).37p<0.61Mixed Models Analysis

Publications (3)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.