A Study to Determine the Clinical Safety/Tolerability and Exploratory Efficacy of EHT 0202 as Adjunctive Therapy to Acetylcholinesterase Inhibitor in Mild to Moderate Alzheimer's Disease
A Study to Determine the Clinical Safety/Tolerability and Exploratory Efficacy of EHT 0202 as Adjunctive Therapy to Acetylcholinesterase Inhibitor in Mild to Moderate Alzheimer's Disease
The objective of this 3-month study is to assess the safety and efficacy of EHT 0202 in
 addition to acetylcholinesterase inhibitor in patients suffering from Alzheimer's Disease.
The aim of this pilot study is to assess the safety and tolerability profile of 2 doses of
 EHT 0202 (40 mg and 80 mg b.i.d) versus placebo in addition to a treatment with
 acetylcholinesterase inhibitor and its exploratory efficacy on cognition, behavior,
 activities of daily living, caregiver's burden and patient's global assessment, during a
 3-month treatment period.
Inclusion Criteria:

 -  Ambulatory male or female patient, aged 60-90 years old included at screening, and
 living at home.

 -  Patient having a clinical diagnosis of probable AD according to National Institute of
 Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related
 Disorders Association (NINCDS-ADRDA) criteria.

 -  Mild to moderate AD with a MMSE total score ≥ 12 and ≤ 24 at screening.

 -  Written informed consent obtained from the patient or, if appropriate, from legal
 representative according to local laws and regulations. The caregiver will also have
 to sign a specific informed consent form regarding his/her participation in the study.

 -  Patient treated for AD treatment with one AChEI (donepezil, galantamine, or
 rivastigmine), according to the recommended posology mentioned in the summary of
 product characteristics, for at least 3 months and with a stable dose for at least 2
 months prior to screening. The dose should be kept unchanged throughout the study
 duration.

 -  Patient with a cerebral CT-scan or cerebral MRI compatible with AD diagnosis, with no
 brain lesions that may be related to another diagnosis and that could be responsible
 for the current patient's condition (ex, but not limited to, non-AD dementia, brain
 injury, brain tumour, stroke, normal pressure hydrocephalus,…). A cerebral CT-scan or
 cerebral MRI has to be performed and results have to be available prior patient's
 randomization if the results of the brain imagery performed to settle the AD diagnosis
 are not available in the patient's file. Brain imaging has also to be performed if
 considered necessary by the investigator, such as in case of emerging neurological
 symptoms or in case of worsening of existing neurological symptoms.

 -  Neurological exam without any particularities or without any specific focal signs
 likely to be related to other conditions than AD.

 -  No contra-indication to AChEI treatment and absence of significant adverse events
 considered to be related to AChEI treatment at screening and randomisation.

 -  Patient and patient's caregiver able to comply with study procedures, notably
 regarding the drug intake at the end of the meal which has to be supervised by the
 caregiver or another competent person.

 Exclusion Criteria:

 -  Diagnosis of vascular dementia according to NINDS-AIREN criteria, or other non-AD
 dementia, or CNS pathology (including but not limited to brain injury, brain tumour,
 stroke, normal pressure hydrocephalus, Parkinson's disease, epilepsy,multiple
 sclerosis,…) that may be responsible for dementia.

 -  Clinically significant pathology and/or uncontrolled condition, including but not
 limited to cancer, infectious (like AIDS), gastro-intestinal, hepatic, renal,
 respiratory, endocrine(like diabetes mellitus, thyroiditis) pathology.

 -  History or current clinically significant psychiatric pathology (including but not
 limited to psychotic disorders, bipolar disorder, personality disorders) that may
 interfere with study assessments.

 -  Current major depressive disorder, either treated or not, associated with clinically
 significant symptoms.

 -  Low blood level of vitamin B12, TSH levels out of normal range at screening.

 -  Current forbidden medication intake or intake within 2 weeks prior to screening.

 -  Recent history (within the past year prior to inclusion) or current cardiovascular
 pathology and/or symptoms considered as clinically significant, including but not
 limited to angina pectoris, uncontrolled arrhythmia, significant ECG abnormalities.
 Lifetime history of heart failure, myocardial infarction, severe and/or uncontrolled
 angina pectoris,and/or ventricular arrhythmia disqualifies the patient.

 -  History or presence of clinically conditions that may interfere with product
 metabolism or with study assessments.

 -  Systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 90 mmHg at
 screening and/or randomisation.

 -  QTc interval (Bazett's correction) ≥ 430 msec for male and ≥ 450 msec for female at
 screening.

 -  Laboratory values (biochemistry, haematology, urinalysis) considered as clinically
 significant and/or that may interfere with study assessments, according to the
 investigator.

 -  ALAT, ASAT, ALP > 2.5 times the upper normal limit (UNL), total bilirubin > 1.5 UNL or
 history of significant liver pathology including hepatitis caused by drugs, HBV, HCV.

 -  BUN, creatinin > 1.5 UNL.

 -  Current or recent history of drug or alcohol abuse or dependence.

 -  Patient not registered at "Sécurité Sociale".

 -  Participation in another study within 1 month prior to screening and during the whole
 duration of the study.