Double-Blind, Parallel-Group Comparison of 23 mg Donepezil SustainedRelease to 10 mg Donepezil Immediate Release in Patients with Moderate toSevere Alzheimer’s Disease - E2020-G000-326

• Conditions: Alzheimer's Disease; MedDRA version: 9.1Level: LLTClassification code 10001896Term: Alzheimer's disease

• Registration Number: EUCTR2006-004888-54-DE
• Lead Sponsor: Eisai Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-01-12
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

9.2 INCLUSION CRITERIA

9.2.1 Inclusion Criteria for Patients

6) Stable Aricept® dose of 10 mg IR (or 10 mg dose of generic donepezil bioequivalent to Aricept®), taken as a single, daily dose for = 3 months prior to the Screening visit. Tablets must not be broken or crushed. Any patient who splits daily doses (for example, Aricept® taken as two daily 5 mg doses instead of a single 10 mg dose) will not beenrolled in the study.

7) Cranial image: no evidence of focal disease to account for dementia on any cranial image (MRI or CT) obtained within 12 months prior to Baseline. If no cranial image (MRI or CT) obtained within 12 months prior to Baseline is available, an attempt should be made to obtain the cranial image with contrast (CT and MRI), unless the use of contrast is clinically contra-indicated.

8) Degree of dementia: MMSE score 1 to 20 at Screening and Baseline

10) SIB = 90 at both Screening and Baseline. Patients will be allowed to re-screen at a later time if their SIB scores are borderline (after 3 months if these scores are 91 or 92, or after 6 months if these scores are 93 or 94) (revised per amendment 04). At re-screening a new patient ID number will be assigned to these patients, and all screening assessments will be repeated.

13) Specified doses of SSRIs are allowed in the study. Patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) at doses that are less than or equal to the approved dose range of therapeutic efficacy as specified in the Physician’s Desk Reference or regional equivalent may enter the study provided that the SSRI dose has been stable for at least 3 months prior to Screening. (Added per Amendment 03).

14) Co-morbid medical conditions must be well-controlled and the patient maintained on stable doses of medications for 3 months. Patients with risk factors of hypertension and cardiac disease may be enrolled in the study, provided that hypertension is controlled by medication in the clinical judgement of the investigator(supine diastolic BP < 95 mm Hg) and cardiac disease (e.g. angina pectoris, congestive heart failure or right bundle branch block is stable on appropriate medication for 3 months prior to Screening. Peripheral vascular disease must have been stable for 3 months prior to Screening.

16) Patients whose serum B12 levels at Screening are below the normal range may nonetheless be admitted to the study if they subsequently show normal levels prior to Baseline. Patients who are receiving Vitamin B12 supplements should maintain a stable dose/regimen throughout the study.

18) Concomitant Medications: Patients undergoing treatment with the following medications may be enrolled in the study provided these conditions are met:
a) Chronic daily benzodiazepine use may be allowed if doses are stable within
approved dose range consistent with currently accepted standards of practice for at
least 1 year prior to screening, to be confirmed by Medical Monitor. Chronic
intermittent use of benzodiazepines may be allowed pending consultation and
approval by the Medical Monitor but not within 48 hours of scheduled assessment.
b). Bronchodilator medications for treatment of COPD may be allowed as long as
drug is administered via metered dose inhaler within approved dose range.
c). Memantine is allowed if taken at prescribed doses that are less than or equal to
20mg/day, provided that the dose has been stable for at least 3months prior to Screening.
d) Additional prescr

Exclusion Criteria

9.3 EXCLUSION CRITERIA
9.3.1 Exclusion Criteria for Patients

1) Patients taking (a) no medication for Alzheimer’s disease, (b) Aricept® or bioequivalent generic donepezil at doses other than 10 mg daily, or 10 mg for < 3 months before Screening; (c) other medications for Alzheimer’s disease, with the following exceptions (Revised per Amendment 02):

a. Memantine is allowed if taken at prescribed doses up to 20 mg/day provided the dose has been stable for at least 3 months prior to Screening.

b. Vitamin E and/or fish oil and/or gingko bilboa are allowed if the doses have been stable for at least 3 months prior to the Screening visit, provided that doses are not changed during the study. Patients undergoing any alternative medical techniques such as acupuncture or acupressure, specifically for the treatment of AD are not eligible to participate in this study.

3) Patients who have no measurable concentrations of donepezil in blood samples collected at Screening (Corrected per Amendment 02).

5) Patients with psychiatric disorders affecting the ability to assess cognition such as
schizophrenia, bipolar or unipolar depression. Patients with clinically significant
sleep disorders will also be excluded unless these are controlled by treatment and
clinically stable for > 3 months prior to screening.

6) Patients with dementia complicated by other organic disease or Alzheimer’s disease with delirium (DSM IV 290.30 or 290.11; Appendix 5).

7) Patients with drug or alcohol abuse or dependence within the past 5 years according to DSM IV criteria (Appendix 5).

8) Patients with any active or clinically significant conditions affecting absorption,
distribution, or metabolism of the study medication (eg, inflammatory bowel disease,
gastric or duodenal ulcers, hepatic disease, or severe lactose intolerance).

9) Patients with evidence of clinically significant, active gastrointestinal, renal, hepatic, respiratory, endocrine, or cardiovascular system disease (Revised per Amendment 02)

10) Patients with a history of malignant neoplasms (does not include basal or squamous cell carcinoma of the skin) treated within 5 years prior to study entry, current evidence of malignant neoplasm, recurrent, metastatic disease. Males with localized prostate cancer requiring no treatment would not be excluded.

12) Donation of blood or blood products during 30 days prior to Screening or plans to
donate blood while participating in the study or within 30 days after completion of the study.

13) Patients who are unwilling or unable to fulfill the requirements of the study.

14) Known hypersensitivity to acetylcholinesterase inhibitors or memantine (Revised per Amendment 01).

15) Use of any prohibited prior or concomitant medications as described in Section 10.7 and listed in Appendix 4

16) Any condition that would make the patient, in the opinion of the investigator,
unsuitable for the study.

17) Involvement in any other investigational drug clinical trial during the preceding
3 months, or likely involvement in any other such trial during the course of this study

18) Patients taking concomitant antidepressant medication known to have significant
anticholinergic effects, such as tricyclic antidepressants prescribed at doses recommended.for the treatment of major depression. Prohibited antidepressants are listed in Appendix 4 (Added per Amendment 02).

19) Patients who cannot swallow or who have difficult swallowing whole tablets. (Added per Amendment 02).

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Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified