A 12-week, open label, multicentre study assessing the efficcay and of Donepezil in patients discontinuing treatment with Memantine monotherapy

• Register: EUCTR
• Last refreshed on: 24 April 2012
• Main ID: EUCTR2004-004918-17-DE
• Date of registration: 05/12/2005
• Prospective Registration: Yes
• Primary sponsor: Pfizer Limited
• Public title: A 12-week, open label, multicentre study assessing the efficcay and of Donepezil in patients discontinuing treatment with Memantine monotherapy
• Scientific title: A 12-week, open label, multicentre study assessing the efficcay and of Donepezil in patients discontinuing treatment with Memantine monotherapy
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-004918-17
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Czech Republic, Finland, Germany, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Patients aged 50 years or over, both men and women. Women of childbearing potential or <2 year post-menopausal must be practising an approved method of contraception and have negative serum b-HCG at screening (women who are breastfeeding are excluded).
Written informed consent to participation.
Patients with moderate to severe Alzheimer’s disease with an MMSE score between 5-17 (inclusive) at screening.
Diagnostic evidence of probable or possible Alzheimer’s disease consistent with DSM-IV and NINCDS-ADRDA criteria made by the site physician at the time of the screening visit. This evidence must be fully documented in the patient’s file prior to the baseline visit.
CT or MRI within the last 18 months consistent with a diagnosis of Alzheimer’s disease without any other clinically significant co-morbid pathologies found. If there has been a significant change in clinical status suggestive of stroke or other possible neurological disease with onset between the time of the last CT or MRI and the screening evaluation, the scan should be repeated if considered appropriate by the investigator.
The patient must be capable of completing all procedures scheduled during the screening and baseline visits including all efficacy parameters (i.e. psychometric tests).
Patients must have a reliable caregiver or family member who agrees to accompany the patient to all clinic visits, provide information about the patient as required by the protocol, and ensure compliance with the medication schedule.
The patient must be currently taking memantine at the recommended dose (10 mg bid) for at least 3 months prior to the screening visit and maintained until the baseline visit.
Treatment of the patient with memantine is judged by the clinician at the time of screening as lacking efficacy or not well tolerated.
Clinical laboratory values within normal limits, and within the sponsor’s guidelines, or, if abnormal, considered and documented as not clinically significant by the investigator.
Health: otherwise healthy and ambulatory or ambulatory-aided (i.e., walker, cane or wheelchair). Vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for compliance with testing procedures.
Patients with stable insulin-dependent diabetes or diabetes stabilized by diet and/or oral hypoglycaemic agents are eligible provided they are monitored regularly to ensure adequacy of control. Patients with known diabetes should have an HbA1C of < 10% at screening.
Patients with controlled hypertension (sitting diastolic BP < 95 mmHg), right bundle branch block (complete or partial), and pacemakers may be included in the study.
Patients with thyroid disease may also be included in the study provided they are euthyroid and stable on treatment for at least 3 months prior to screening. Stable treatment must be maintained throughout the study.
Patients with vitamin B12 deficiency who are on a stable dose of medication for at least 3 months prior to screening, and who have normal serum B12 levels at screening, will be eligible. This stable dose must be maintained throughout the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients with a known hypersensitivity to donepezil, piperidine derivatives, or any of the excipients used in the formulation of donepezil
Patients with active or clinically significant conditions affecting absorption, distribution or metabolism of the study medication.
Patients who have been treated with a cholinesterase inhibitor in the 3 months prior to screening visit.
Patients treated with any investigational drug within 30 days of screening visit.
Patients without a reliable caregiver, or patients or caregivers who are unwilling or unable to complete any of the outcome measures and fulfill the requirements of this study.
Nursing home patients will be excluded from entering the study. Likewise, patients for whom institutionalization is being considered within the next 3 months should also be excluded.
Patients with clinically significant obstructive pulmonary disease or asthma.
Patients with a recent (< 2 years) haematologic/oncologic disorders.
Evidence of active clinically significant and unstable gastrointestinal, endocrine or cardiovascular system disease.
Evidence of severe hepatic or renal impairment.
Patients with a current DSM-lV diagnosis of Major Depressive Disorder (MDD), or any current primary psychiatric diagnosis other than Alzheimer’s disease (as per DSM-lV). Patients who, in the judgment of the investigator, represent a suicide risk.
Patients with dementia complicated by other organic disease or Alzheimer’s disease with delirium (DSM 290.30 or 290.11) are excluded. Depression or delusions are common in Alzheimer’s disease, but patients with pronounced severe symptoms such that they warrant an alternative concurrent diagnosis, should be excluded.
Patients with a known or suspected history of alcoholism or drug abuse (within the past 10 years).
Any condition which would make the patient or the caregiver, in the opinion of the investigator or sponsor, unsuitable for the study.
Patients who have taken or are taking any unapproved prior or concomitant medication as defined in the protocol.
Patients with a history of seizures or seizure disorders.
Patients must be able to swallow tablet medication. No crushing of tablets is allowed.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alzheimer's disease
MedDRA version: 7 Level: VTc Classification code 10012271

Intervention(s)

Product Name: Aricept (donepezil hydrochloride)
Product Code: E2020
Pharmaceutical Form: Tablet
INN or Proposed INN: donepezil
Current Sponsor code: E2020
Other descriptive name: 2,3-dihydro-5,6-dimethoxy-2-{[1-(phenylmethyl)-4-piperidinyl] methyl}-1H-inden-1-one hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Aricept (donepezil hydrochloride)
Product Code: E2020
Pharmaceutical Form: Tablet
INN or Proposed INN: donepezil
Current Sponsor code: E2020
Other descriptive name: 2,3-dihydro-5,6-dimethoxy-2-{[1-(phenylmethyl)-4-piperidinyl] methyl}-1H-inden-1-one hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: To evaluate the efficacy of donepezil on cognition (MMSE) in patients who are currently being treated with memantine, and are switched to donepezil because treatment with memantine is lacking efficacy or is not well tolerated.

Secondary Objective: To evaluate the effects of donepezil on other clinically relevant measures including behaviour (NPI), physician and caregiver satisfaction/ease of use, global function (CGI-I), social behaviour (Caregiver Diary), safety and tolerability in this patient group.

Primary end point(s): Mini Mental State Examination (MMSE): The MMSE is a brief test to assess the cognitive status of the patient. The 30-point test includes items that evaluate orientation to time and place, immediate and delayed recall, attention and language. The MMSE will be administered by the same trained rater at each visit.

Secondary ID(s)

A2501046

2004-004918-17-FI