Alzheimer Disease
Conditions
Keywords
DAT Study
Brief summary
The objective of this trial is the global risk-benefit assessment of Cerebrolysin as compared to donepezil in patients with mild to moderate dementia of Alzheimer's Type (DAT). In addition, a traditional approach will be taken based on the evaluation of the separate risk and benefit domains in comparison with donepezil. Global risk-benefit as compared to donepezil will be analyzed by determining whether the Cerebrolysin group shows a statistically significant non-inferiority with regard to the combined primary safety and efficacy endpoints (weighted multivariate ensemble). The endpoints will be combined by a global multivariate non-parametric procedure, weighting the safety and efficacy part 50:50.
Detailed description
This phase IIIb/IV trial involves patients with mild to moderate Alzheimer's Disease in Europe, Canada and Latin America and is designed as a prospective, randomized, double-blind, active-controlled, parallel-group, multicenter, double-dummy trial. The study endpoint is after 24 weeks. In total, five visits are scheduled in this trial and a follow-up phone call is performed 4 weeks after Visit 5 (Week 24). The first visit (Screening Visit, Visit 1) identifies participants who are eligible for and interested in this trial.Efficacy and safety parameters are assessed at the Baseline Visit (Visit 2), in Week 6-7 (Visit 3), Week 14-15 (Visit 4) and Week 24 (Visit 5).
Interventions
DRUGCerebrolysin
Intravenous medication is given in three treatment courses (TC). Each treatment course lasts for two weeks and consists of 10 infusions (5 infusions weekly). The first treatment course (TC 1) will be in Week 1 and 2, second treatment course (TC 2) will be repeated during Week 9 and 10 and third treatment course (TC 3) during Week 19 and 20. Placebo for donepezil:1 tablet per day from TC 1 Day 1 on and 2 tablets per day from Visit 3 - Visit 5, p.o.
DRUGDonepezil
5-10 mg donepezil: 1x5 mg donepezil as 1 tablet per day from TC 1 Day 1 on and 2x5 mg donepezil as 2 tablets from Visit 3- Visit 5, p.o. Intravenous medication is given in three treatment courses (TC). Each treatment course lasts for two weeks and consists of 10 infusions (5 infusions weekly). The first treatment course (TC 1) will be in Week 1 and 2, second treatment course (TC 2) will be repeated during Week 9 and 10 and third treatment course (TC 3) during Week 19 and 20.
Sponsors
Ever Neuro Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients ≥50 years of age * Diagnosis of probable mild to moderate Alzheimer's disease according to DSM-IV-TR and NINCDS-ADRDA criteria (see section 18.2.1) * Screening MMSE score between 15 and 24, both inclusive * Modified Hachinski Ischemic score of ≤4 * Hamilton Depression Scale score ≤10 * Brain computerized tomography (CT) or brain magnetic resonance imaging (MRI) scans within 12 months prior to screening without evidence of infection, infarction, or other focal lesions and without clinical symptoms suggestive of intervening neurological disease. If no brain CT or brain MRI is available, a brain MRI shall be performed to exclude other causes of dementia-like syndromes. * Sufficient language skills to complete all testing without assistance of a language interpreter * Ability to perform all sections of the ADAS-cog * Good general health without additional diseases expected to interfere with the study * Normal B12, folic acid, VDRL, and TSH or without any clinically significant laboratory abnormalities that would be expected to interfere with the study. * ECG and chest x-ray (if available) without clinically significant laboratory abnormalities that would be expected to interfere with the study. * Patient is not of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile) * Responsible caregiver (individual who continuously attends to the needs of the person or dependent adult), who agrees to be present during study conduct. * Written informed consent obtained from the patient and caregiver (and legally authorized representative or guardian if different from caregiver) prior to entry into the study (Screening Visit)
Exclusion criteria
* Any abnormalities associated with significant central nervous disease other than Alzheimer's Disease * Severe psychotic features, confusion, agitation or behavioral problems within the last three months that could lead to difficulties complying with the protocol * Delusional symptoms are often characteristic of Alzheimer's disease, but patients with symptoms so pronounced that they warrant an alternative psychiatric diagnosis are excluded * History of alcohol or substance abuse or dependence within the past two years (DSM-IV-TR criteria, see also sections 18.3.1 and 18.3.2) * History of schizophrenia, schizoaffective disorder, bipolar affective disorder (DSM-IV-TR criteria) * History of newly identified major depressive disorder within eight weeks before Screening Visit (DSM-IV-TR) (see also
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in ADAS-cog. and CIBIC+ score distribution | at Week 24 | The ADAS-cog is a psychometric instrument that evaluates cognitive impairment in the assessment of Alzheimer's disease (memory, attention, reasoning, language, orientation and praxis). The CIBI+ is a global rating measure which covers the categories general, mental/cognitive state, behavior, and activities of daily living. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | at Week 24 | descriptive analysis of number, intensity, relation to study medication and action taken |
| Vital signs | at Week 24 | descriptive analysis of baseline-changes of blood pressure, heart rate, respiration rate, body temperature and weight |
| Laboratory tests | at Week 24 | descriptive analysis of baseline-changes of hematology (e.g. red blood cell count, hematocrit, hemoglobin levels, mean corpuscular volume, mean corpuscular hemoglobin), blood chemistry (e.g. glucose, total cholesterol, high density lipoprotein cholesterol) and urinalysis (glucose, bilirubin, ketones, density, blood, pH, protein, nitrites and leukocytes) |
Countries
Austria
Outcome results
None listed