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 (EHT0202/002)

This study has been completed.
Sponsor:
Information provided by:
Exonhit
ClinicalTrials.gov Identifier:
NCT00880412
First received: April 10, 2009
Last updated: September 18, 2009
Last verified: September 2009
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: EHT 0202 etazolate
Drug: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Exonhit:

Primary Outcome Measures:
  • 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. [ Time Frame: all study visits ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: at the end of the 3-month study treatment period ] [ Designated as safety issue: No ]

Enrollment: 197
Study Start Date: April 2008
Study Completion Date: August 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EHT 0202 40 mg bid
study treatment is given in addition to one acetylcholinesterase inhibitor (galantamine, rivastigmine or donepezil)
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.
Other Names:
  • EHT 0202
  • etazolate
Experimental: EHT 0202 80 mg bid
study treatment is given in addition to one acetylcholinesterase inhibitor (galantamine, rivastigmine or donepezil)
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.
Other Names:
  • EHT 0202
  • etazolate
Placebo Comparator: placebo bid
study treatment is given in addition to one acetylcholinesterase inhibitor (galantamine, rivastigmine or donepezil)
Drug: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   60 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00880412

Locations
France
Hôpital Privé Les Magnolias
Ballainvilliers, France, 91160
Cabinet Médical
Bergerac, France, 24100
Fleyriat Hospital
Bourg en Bresse, France, 01012
Cabinet Médical
Dijon, France, 21000
Charles Foix Hospital
Ivry sur Seine, France, 94026
Cabinet Médical
La Seyne sur Mer, France, 83500
Roger Salengro Hospital
Lille, France, 59037
Dupuytren Hospital
Limoges, France, 87042
Clinique Léopold Bellan
Magnanville, France, 78200
Cabinet Médical 2
Montpellier, France, 34080
Cabinet Médical
Montpellier, France, 34070
CHU Nantes Hôpital Laennec
Nantes, France, 44093
Cabinet Médical
Nice, France, 06000
Cabinet Médical 2
Nice, France, 06000
CHU Cochin Broca
Paris, France, 75013
Cabinet Médical
Rambouillet, France, 78120
CHU Rennes
Rennes, France, 35033
Cabinet Médical
Rodez, France, 12000
Cabinet Médical
Rueil Malmaison, France, 92500
Cabinet Médical
Saint Brieuc, France, 22000
Cabinet Médical
Toulon, France, 83000
Purpan-Casselardit Hospital - University of Toulouse
Toulouse, France, 31059
Sponsors and Collaborators
Exonhit
Investigators
Principal Investigator: Bruno Vellas, MD Casselardit Hospital - University of Toulouse
  More Information

No publications provided

Responsible Party: Professor Bruno Vellas, MD, University of Toulouse - Purpan - Casselardit Hospital
ClinicalTrials.gov Identifier: NCT00880412     History of Changes
Other Study ID Numbers: EHT0202/002
Study First Received: April 10, 2009
Last Updated: September 18, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Exonhit:
safety
efficacy
Alzheimer's disease
treatment
phase II
study
cholinesterase inhibitor

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Etazolate
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Phosphodiesterase Inhibitors
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs

ClinicalTrials.gov processed this record on August 20, 2014