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

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 1)
• Mini Mental State Examination (MMSE) > 24 and 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 170mmHg or diastolic pressure > 100mmHg)
• Bradycardia (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