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Cerebrolysin Compared to Donepezil in Patients With Mild to Moderate Dementia of Alzheimer's Type (DAT) (DAT)

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ClinicalTrials.gov Identifier: NCT01822951
Recruitment Status : Withdrawn
First Posted : April 4, 2013
Last Update Posted : October 26, 2015
Sponsor:
Information provided by (Responsible Party):
Ever Neuro Pharma GmbH

Tracking Information
First Submitted Date  ICMJE March 25, 2013
First Posted Date  ICMJE April 4, 2013
Last Update Posted Date October 26, 2015
Study Start Date  ICMJE Not Provided
Estimated Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 3, 2014)
Change from Baseline in ADAS-cog. and CIBIC+ score distribution [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 28, 2013)
  • Change from Baseline in ADAS-cog. [ Time Frame: at Week 24 ]
  • CIBIC+ score distribution [ Time Frame: at Week 24 ]
  • Proportion of patients with premature discontinuation due to adverse events [ Time Frame: during the first 24 Weeks ]
  • Proportion of patients with serious adverse events [ Time Frame: during the first 24 Weeks ]
  • Proportion of patients with adverse events [ Time Frame: during the first 24 Weeks ]
Change History Complete list of historical versions of study NCT01822951 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 3, 2014)
  • Adverse events [ Time Frame: at Week 24 ]
    descriptive analysis of number, intensity, relation to study medication and action taken
  • Vital signs [ Time Frame: at Week 24 ]
    descriptive analysis of baseline-changes of blood pressure, heart rate, respiration rate, body temperature and weight
  • Laboratory tests [ Time Frame: 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)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 28, 2013)
  • Number of ADAS-cog. responders [ Time Frame: at Visit 3 (Week 6-7), Visit 4 (Week 14-15), Visit 5 (Week 24), Visit 6 (Week 39) and Visit 7 (Week 52) ]
    ADAS-cog. responders are evaluated by dichotomization of the ADAS-cog. changes from Baseline at the benchmark -4 (responder = improvement by at least 4 score points)
  • Number of ADAS-cog.+ responders [ Time Frame: at Visit 3 (Week 6-7), Visit 4 (Week 14-15), Visit 5 (Week 24), Visit 6 (Week 39) and Visit 7 (Week 52) ]
    ADAS-cog.+ responders are evaluated by dichotomization of the ADAS-cog. changes from Baseline at the benchmark -4 (responder = improvement by at least 4 score points)
  • Number of CIBIC+ responders [ Time Frame: at Visit 3 (Week 6-7), Visit 4 (Week 14-15), Visit 5 (Week 24), Visit 6 (Week 39) and Visit 7 (Week 52) ]
    CIBIC+ responders are evaluated by dichotomization of the CIBIC+ scale at the benchmark 4 (responder = CIBIC+ < 4)
  • Adverse events [ Time Frame: at Week 24 ]
    descriptive analysis of number, intensity, relation to study medication and action taken
  • Vital signs [ Time Frame: at Week 24 ]
    descriptive analysis of baseline-changes of blood pressure, heart rate, respiration rate, body temperature and weight
  • Laboratory tests [ Time Frame: 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)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cerebrolysin Compared to Donepezil in Patients With Mild to Moderate Dementia of Alzheimer's Type (DAT)
Official Title  ICMJE Comparison of Cerebrolysin and Donepezil: A Randomized, Double-blind, Controlled Trial on Efficacy and Safety in Patients With Mild to Moderate Alzheimer's Disease
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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE
  • Drug: Cerebrolysin

    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.

    Other Name: Cognicer, Renacenz
  • Drug: Donepezil

    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.

    Other Names:
    • Other names:
    • e.g. Aricept, Donesyn
Study Arms  ICMJE
  • Experimental: Cerebrolysin Verum

    Intravenous medication is given in three treatment courses (TC). Each treatment course lasts for two weeks and consists of 10 infusions (5 infusions weekly). For the infusion 2x10 ml Cerebrolysin (215.2 mg/ml) is diluted with 80 ml 0.9% NaCl (saline) to a total volume of 100 ml, i.v.

    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.

    Intervention: Drug: Cerebrolysin
  • Active Comparator: Donepezil Verum

    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.

    Placebo for Cerebrolysin: 100 ml 0.9% NaCl (saline), i.v. infusion. Intravenous medication is given in three treatment courses (TC). Each treatment course lasts for two weeks and consists of 10 infusions (5 infusions weekly).

    Intervention: Drug: Donepezil
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: October 23, 2015)
0
Original Estimated Enrollment  ICMJE
 (submitted: March 28, 2013)
510
Estimated Study Completion Date  ICMJE December 2016
Estimated Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 exclusion criteria 11 and inclusion criteria 5)
  • Any significant systemic illness or unstable medical condition that could lead to difficulties complying with the protocol. Patients with a history of systemic cancer within the past two years are excluded
  • History of myocardial infarction in the past year or unstable or severe cardiovascular disease, including uncontrolled hypertension
  • Any clinically significant laboratory abnormalities on the battery of screening tests (hematology, blood chemistry, urinalysis, ECG, chest x-ray (if available))
  • Uncontrolled insulin-requiring diabetes or non-insulin dependent diabetes mellitus (HbA1c >10.0)
  • Use of any concomitant medication that could affect functioning of the CNS or interfere with efficacy assessment.
  • Patients who in the Investigator's opinion would not comply with study procedures
  • Patients with fragile or thin veins who may not be able to receive many i.v. infusions
  • Patients who in the past have not tolerated treatment with 10 mg donepezil or treatment with a corresponding dose of another cholinesterase inhibitor
  • Patients with history of any epileptic seizure
  • Patients with known or suspected hypersensitivity to Cerebrolysin, donepezil hydrochloride, piperidine derivates or any of the IMPs' excipients
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01822951
Other Study ID Numbers  ICMJE EVE-AT-0412
2012-004944-31 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ever Neuro Pharma GmbH
Study Sponsor  ICMJE Ever Neuro Pharma GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Dieter Meier, MD Ever Neuro Pharma GmbH
PRS Account Ever Neuro Pharma GmbH
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP