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

NCT01822951 | Withdrawn Phase 4 DMC

• 2 other identifiers: EVE-AT-04122012-004944-31
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Keywords

DAT Study

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in ADAS-cog. and CIBIC+ score distribution

  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.

  at Week 24

Secondary Outcomes (3)

• Adverse events

  at Week 24

• Vital signs

  at Week 24

• Laboratory tests

  at Week 24

Study Arms (2)

Cerebrolysin Verum

EXPERIMENTAL

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.

Drug: Cerebrolysin

Donepezil Verum

ACTIVE COMPARATOR

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).

Drug: Donepezil

Interventions

Cerebrolysin DRUG

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.

Also known as: Cognicer, Renacenz

Cerebrolysin Verum

Donepezil DRUG

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.

Also known as: Other names:, e.g. Aricept, Donesyn

Donepezil Verum

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Ever Neuro Pharma GmbH: lead

Study Sites (1)

AKh Allgemeines Krankenhaus der Stadt Linz GmbH

Linz, 4021, Austria

Location

Related Publications (7)

• Alvarez XA, Cacabelos R, Laredo M, Couceiro V, Sampedro C, Varela M, Corzo L, Fernandez-Novoa L, Vargas M, Aleixandre M, Linares C, Granizo E, Muresanu D, Moessler H. A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer's disease. Eur J Neurol. 2006 Jan;13(1):43-54. doi: 10.1111/j.1468-1331.2006.01222.x.

  PMID: 16420392 BACKGROUND

• Panisset M, Gauthier S, Moessler H, Windisch M; Cerebrolysin Study Group. Cerebrolysin in Alzheimer's disease: a randomized, double-blind, placebo-controlled trial with a neurotrophic agent. J Neural Transm (Vienna). 2002 Jul;109(7-8):1089-104. doi: 10.1007/s007020200092.

  PMID: 12111446 BACKGROUND

• Ruether E, Husmann R, Kinzler E, Diabl E, Klingler D, Spatt J, Ritter R, Schmidt R, Taneri Z, Winterer W, Koper D, Kasper S, Rainer M, Moessler H. A 28-week, double-blind, placebo-controlled study with Cerebrolysin in patients with mild to moderate Alzheimer's disease. Int Clin Psychopharmacol. 2001 Sep;16(5):253-63. doi: 10.1097/00004850-200109000-00002.

  PMID: 11552768 BACKGROUND

• Bae CY, Cho CY, Cho K, Hoon Oh B, Choi KG, Lee HS, Jung SP, Kim DH, Lee S, Choi GD, Cho H, Lee H. A double-blind, placebo-controlled, multicenter study of Cerebrolysin for Alzheimer's disease. J Am Geriatr Soc. 2000 Dec;48(12):1566-71. doi: 10.1111/j.1532-5415.2000.tb03865.x.

  PMID: 11129744 BACKGROUND

• Alvarez XA, Cacabelos R, Sampedro C, Aleixandre M, Linares C, Granizo E, Doppler E, Moessler H. Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin. Eur J Neurol. 2011 Jan;18(1):59-68. doi: 10.1111/j.1468-1331.2010.03092.x.

  PMID: 20500802 BACKGROUND

• Xiao S, Yan H, Yao P. Efficacy of Cerebrolysin in patients with Alzheimer's disease. Clin. Drug Invest. 2000; 19:43-53.

  BACKGROUND

• Ruther E, Ritter R, Apecechea M, Freytag S, Windisch M. Efficacy of the peptidergic nootropic drug cerebrolysin in patients with senile dementia of the Alzheimer type (SDAT). Pharmacopsychiatry. 1994 Jan;27(1):32-40. doi: 10.1055/s-2007-1014271.

  PMID: 8159781 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

cerebrolysin; Donepezil

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• Dieter Meier, MD

  Ever Neuro Pharma GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2013
• First Posted: April 4, 2013
• Primary Completion: September 1, 2016
• Study Completion: December 1, 2016
• Last Updated: October 26, 2015

Record last verified: 2015-10

Locations

AU (1)