Double-Blind, Parallel-Group Comparison of 23 mg Donepezil SR to 10 mg Donepezil IR in Patients with Moderate to Severe Alzheimer?s disease - E2020-G000-326

• Conditions: Severe Alzheimer disease; MedDRA version: 6.1Level: PTClassification code 10012271

• Registration Number: EUCTR2006-004888-54-IT
• Lead Sponsor: EISAI LTD UK

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-09-07
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1600

Inclusion Criteria

1) Written informed consent will be obtained from the patient (if possible) or from the patient?s legal guardian or other representative prior to beginning screening activities. Even if unable to provide written informed consent, the patient must assent verbally to participating in the study and the record should note this assent. The caregiver must separately give informed consent for his or her own participation in the study. 2) Age range: Adult patients, 45 to 90 years of age inclusive 3) The caregiver must separately meet the specified inclusion/exclusion criteria for caregivers (Section 9.2.2 and Section 9.3.2). 4) Gender distribution: men and women. Women must be of non-child-bearing potential (> 1 year post-menopausal or surgically sterile). 5) Diagnosis: diagnostic evidence of probable AD consistent with DSM-IV 290.00 or 290.10 and NINCDS-ADRDA criteria (Appendix 5 and Appendix 6, respectively) 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 more than 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 be enrolled in the study. (Revised as per Amendment 02) 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 (Revised as per Amendment 02) 8) Degree of dementia: MMSE score minor/equal to 20 at Screening and Baseline 9) CSDD < 12 at Screening (Revised as per Amendment 02) 10) SIB minor/equal to 90 at both Screening and Baseline (Renumbered as per Amendment 2) 11) Health: physically healthy and ambulatory or ambulatory-aided (ie, walker or cane); Corrected vision and hearing sufficient for compliance with testing procedures, and able to read pre-morbidly (Revised as per Amendment 02) 12) Clinical laboratory values must be within normal limits or, if abnormal, must be judged not clinically significant by the investigator (Renumbered as per Amendment 02). 13) Patients undergoing treatment with selective serotonin reuptake inhibitors (SSRI)(< 20 mg daily of citalopram, < 10 mg daily of escitalopram,fluoxetine, fluvoxamine,< 30 mg daily of paroxetine or <100 mg daily of sertraline) may enter the study provided that the SSRI dose has been stable for at least three months prior to Screening (added as per Amendment 02). 14) Patients with risk factors of hypertension and cardiac disease may be enrolled in the study, provided that hypertension is medication controlled (supine diastolic BP < 95 mm Hg) and cardiac disease (e.g. angina pectoris, congestive heart failure,right bundle branch block, or arrhythmias) is stable on appropriate medication for 3 months prior to Screening. Peripheral vascular disease must have been stable for 3 months prior to Screening. 15) Patients with diabetes mellitus or risk factors for diabetes mellitus may be enrolled in the study provided that the patient?s disease is stable and that there have been no recent (within 3 months of Screening) hospitalizations for diabetic ketoacidosis,hyperosmolar coma, or hypoglycemia (revised as per Amendment 02). Patients with non-insulin-dependent diabetes may enroll in the study if controlled on diet or oral medications. 16) All diabetic patients must have an HbA1c concentration of < 10% and a fasting (8 hours) serum glucose con

Exclusion Criteria

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 as per Amendment 02): a. Memantine is allowed if taken at prescribed doses of 20 mg daily for at least 3 months prior to the Screening visit b. Vitamin E and/or fish oil are allowed if dose has been stable for at least 3 months prior to the Screening visit, provided that doses are not changed during the study 2) No caregiver available to meet the inclusion criteria for caregivers 3) Patients who have no measurable concentrations of donepezil in blood samples collected at Screening (corrected as per Amendment 02) 4) Patients with neurological disorders that affect cognition or the ability to assess cognition but are distinguishable from Alzheimer?s disease, such as Parkinson?s disease, multi-infarct dementia, dementia due to cerebrovascular disease, Huntington?s disease, Pick?s disease, Creutzfeld-Jacob disease, Lewy Body disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, or multiple sclerosis, as well as patients with known human immunodeficiency virus (HIV) disease, neurosyphilis, or a history of significant head trauma followed by persistent neurological deficits or known structural brain abnormalities 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 (revised as per Amendment 01). 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 as 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. 11) Known plan for elective surgery during the treatment period that would require general anesthesia and administration of neuromuscular blocking agents, such as succinylcholine, to induce paralysis/muscle relaxation. Minor surgery, such as colonoscopy or cataract surgery, will be permitted as long as it does not require the use of these paralytic agents. (Revised as per Amendment 02) 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 hypersensitivit

Study & Design

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