| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001896 |
| E.1.2 | Term | Alzheimer's disease |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the clinical safety/tolerability of 2 doses of EHT 0202 (40 and 80 mg b.i.d.) versus placebo as adjunctive therapy to AChEI over a 3-month treatment period in ambulatory patients with mild to moderate probable Alzheimer’s disease. |
|
| E.2.2 | Secondary objectives of the trial |
To assess
- the exploratory clinical efficacy on cognitive functions, activities of daily living, patient’s behaviour, caregiver’s burden and patient’s global assessment
- the population pharmacokinetics (PK)
Pharmacogenomic/pharmacogenetic objectives :
- to define the potential relationship between
treatment response and blood serum sAPPĪ± levels.
treatment response and a predefined blood signature using splice-arrays.
treatment response and ApoE genotyping.
- to establish prospectively blood signatures using splice-arrays on the basis of treatment response profile.
Diagnostic objective :
To assess the sensitivity of a predefined micro-array blood signature for AD diagnosis in the current study population. If deemed necessary, additional exploratory blood signatures for AD diagnosis using splice-arrays may be established on the basis of the study population.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
– Ambulatory male or female patient, aged 60-90 years old included at screening, and living at home.
– Patients 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 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. Cerebral imagery 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. |
|
| E.4 | Principal 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 (see list of forbidden medication).
– 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 who is not registered at “Sécurité Sociale”.
– Participation in another study within 1 month prior to screening and during the whole duration of the study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Assessment of the clinical safety/tolerability in each study group, based on:
– incidence/frequency of adverse events (AE) and serious adverse events (SAE), relation to start of treatment, relation to drug exposure, time to resolution, severity, relationship to study treatment,
– findings at clinical and neurological examinations,
– change from baseline of vital signs, ie. heart rate (HR), blood pressure (BP), including nature and frequency of changes,
– change from selection of weight, including frequency of changes,
– drop-out rate, including reason for withdrawal and time from treatment start,
– change from selection of biological safety parameters, including nature and frequency of changes: blood chemistry also including kidney and liver chemistry, urinalysis, hematology,
– change in ECG parameters including nature and frequency of changes.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
Print
