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

Alzheimer's Disease Clinical Trial

— EHT0202/002  

Official title:

A Pilot, Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicentre, Phase IIA Study to Determine the Clinical Safety/Tolerability and Exploratory Efficacy of EHT 0202 (40 and 80 mg Bid) as Adjunctive Therapy to Acetylcholinesterase Inhibitor Over a 3-month Period in Ambulatory Patients Suffering From Mild to Moderate Alzheimer's Disease (EHT 0202/002 Protocol)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00880412
• Other study ID #: EHT0202/002
• Status: Completed
• Phase: Phase 2
• First received: April 10, 2009
• Last updated: September 18, 2009
• Start date: April 2008
• Est. completion date: August 2009

Study information

• Verified date: September 2009
• Source: Exonhit
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: August 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• EHT 0202 etazolate
In each arm, 2 capsules of study treatment (capsules of EHT0202 40mg and/or placebo) are taken twice a day during breakfast and dinner over a 3-month treatment period. There is non treatment adjustment.
• Placebo
In each arm, 2 capsules of study treatment (capsules of EHT0202 40mg and/or placebo) are taken twice a day during breakfast and dinner over a 3-month treatment period. There is non treatment adjustment.

Locations

Country	Name	City	State
France	Hôpital Privé Les Magnolias	Ballainvilliers
France	Cabinet Médical	Bergerac
France	Fleyriat Hospital	Bourg en Bresse
France	Cabinet Médical	Dijon
France	Charles Foix Hospital	Ivry sur Seine
France	Cabinet Médical	La Seyne sur Mer
France	Roger Salengro Hospital	Lille
France	Dupuytren Hospital	Limoges
France	Clinique Léopold Bellan	Magnanville
France	Cabinet Médical	Montpellier
France	Cabinet Médical 2	Montpellier
France	CHU Nantes Hôpital Laennec	Nantes
France	Cabinet Médical	Nice
France	Cabinet Médical 2	Nice
France	CHU Cochin Broca	Paris
France	Cabinet Médical	Rambouillet
France	CHU Rennes	Rennes
France	Cabinet Médical	Rodez
France	Cabinet Médical	Rueil Malmaison
France	Cabinet Médical	Saint Brieuc
France	Cabinet Médical	Toulon
France	Purpan-Casselardit Hospital - University of Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Exonhit

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	incidence/frequency and severity of adverse events, relation to treatment start and drug exposure, drop-out rate, including reason for withdrawal, clinical examination, change from screening of biological safety parameters, vital signs, ECG and weight.		all study visits	No
Secondary	Assessment of cognition (ADAS-Cog, Neuropsychological Test Battery, MMSE), patient's global functioning (CDR-SB,CGI), patient's behaviour (NPI), daily living activities (ADCS-ADL) and caregiver's burden. Population PK of EHT 0202 and PK/PD profile.		at the end of the 3-month study treatment period	No