EARTH 413: A Study of Aricept in Hispanic Patients With Mild to Moderate Alzheimer's Disease (AD)

Condition(s) targeted: Alzheimer's Disease

Intervention: Aricept (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Eisai Inc.

Official(s) and/or principal investigator(s):
Honglan Li, Study Director, Affiliation: Eisai Inc.

12-week, open-label study to evaluate the effectiveness and safety of donepezil hydrochloride in Hispanic patients with mild to moderate Alzheimer's Disease (AD) in the U. S.

Official title: A 12-Week, Multicenter, Open-Label Study to Evaluate the Effectiveness and Safety of Donepezil Hydrochloride (Aricept) in Hispanic Patients With Mild to Moderate Alzheimer's Disease

Study design: Treatment, Non-Randomized, Open Label, Placebo Control, Single Group Assignment, Efficacy Study

Primary outcome: FOME (Fuld Object Memory Evaluation); SDMT (Symbol Digit Modalities Test); NPI (Neuropsychiatric Inventory); MMSE (the Mini-Mental State Examination).

Minimum age: 50 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

INCLUSION CRITERIA:

- Patients who self-identify as Hispanic and currently live in the United States.

- Age range: Patients >= 50 years.

- Sex distribution: both men and women. Women must be two (2) years post-menopausal or

surgically sterile.

- MMSE scores between 10 and 26 (inclusive).

- Patients must have diagnostic evidence of AD (DSM-IV and NINCDS/ADRDA criteria) either

prior to or at the screening visit. Patients with AD who may also have cerebrovascular disease as evidenced by risk factors such as hypertension, diabetes, elevated cholesterol levels, and smoking are also eligible to enroll in the study. In order to be enrolled, such patients' clinical conditions must be controlled, and it must be the investigator's opinion that the patient's primary diagnosis is AD, not vascular dementia. The diagnosis of AD must be recorded in the patient's clinical record prior to the baseline visit.

- CT or MRI within the last 12 months consistent with a diagnosis of AD without any

other clinically significant comorbid pathologies found. Patients with vascular changes may be included provided that they do not meet NINDS-AIREN criteria for probable Vascular Dementia (VaD). A copy of the report will be required and should be appended to the case report form. If there has been a significant change in clinical status suggestive of stroke or other neurological disease in addition to AD with onset between the time of the last CT or MRI and the screening evaluation, the scan should be repeated during screening.

- All patients must be naïve to Aricept® treatment. Previous use of an approved or

unapproved cholinesterase inhibitor (Exelon® , Cognex®, Reminyl®/Razadyne®, metrifonate, physostigmine) or memantine is allowed provided that the medication was discontinued at least 3 months prior to screening and that the discontinuation was not done for the purpose of enrolling the patient in this trial.

- Patients must reside in the community. (Residence in an assisted living facility is

allowed.)

- 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 caregiver must have a minimum of three days per week of direct contact with the patient (for at least 4 hours per day during waking hours).

- The patient must be capable of reliably completing study assessments including all

efficacy parameters (MMSE, SDMT, and FOME) and all procedures scheduled during the screening, baseline and all follow-up visits.

- Patients must have clinical laboratory values within normal limits, and within the

Eisai (sponsor) guidelines, or abnormalities considered not clinically significant by the investigator and sponsor.

- Patients with stable insulin-dependent diabetes or diabetes stabilized by diet and/or

oral hypoglycemic agents are eligible provided they are monitored regularly to ensure adequacy of control. Patients with known diabetes should have an HbA1c of < 8% 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 also may be included in the study provided they are

euthyroid and stable on treatment for at least 3 months prior to screening, and the stable treatment is maintained throughout study.

- Patients with a history of seizure disorder are allowed provided that they are on

stable treatment for at least 3 months and have not had a seizure within the past 6 months.

- Patients must be able to swallow tablet medication -- no crushing of the tablet is

allowed.

- Patient must be ambulatory or ambulatory-aided (i. e., walker or cane, or wheelchair).

His/her vision and hearing (eyeglasses and/or hearing aid permissible) must be sufficient for compliance with testing procedures.

EXCLUSION CRITERIA:

- Age range: Patients < 50 years.

- MMSE score of < 10 or > 26.

- Patients with active or clinically significant conditions affecting absorption,

distribution or metabolism of the study medication (e. g., inflammatory bowel disease, gastric or duodenal ulcers or severe lactose intolerance).

- Patients with a known hypersensitivity to piperidine derivatives or cholinesterase

inhibitors.

- 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.

- Patients who live in a skilled nursing facility (nursing home) or expect to enter

nursing home within the next 3 months.

- Patients with clinically significant obstructive pulmonary disease or asthma not

controlled with treatment at any time during the previous 3 months.

- Patients with recent (< 2 years) hematological/oncological disorders.

- Evidence of clinically significant, active gastrointestinal, renal, hepatic, endocrine

or cardiovascular system disease.

- Patients with a current DSM-lV diagnosis of Major Depressive Disorder (MDD) or any

current primary psychiatric diagnosis other than AD (as per DSM-lV).

- Patients with dementia complicated by delirium (DSM 290. 30 or 290. 11); depression or

delusions are common in AD, and patients with severe symptoms so pronounced that they warrant an alternative, concurrent diagnosis, are excluded.

- Patients with a known or suspected history of alcoholism or drug abuse (within the

past 5 years).

- Patients with treated vitamin B-12 deficiency who have not been on a stable dose of

medication for at least 3 months prior to the study screening visit and who do not have normal serum B-12 levels at screening.

- Patients with treated hypothyroidism that have not been on a stable dose of medication

for 3 months prior to screening and who do not have normal serum T-4 and TSH at screening.

- Patients with diabetes mellitus controlled by diet, oral medication, or insulin who do

not have an HbA1c of < 8. 0% and a random serum glucose value of < 170 mg/dl.

- Patients previously treated with Aricept® (donepezil Hydrochloride).

- Any condition which would make the patient or the caregiver, in the opinion of the

investigator, unsuitable for the study.

Alzheimer's Disease and Cognitive Disorders Clinic at Barrow Neurology Institute, Phoenix, Arizona 85013, United States

21st Century Neurology, Phoenix, Arizona 85013, United States

Pacific Sleep Medicine Services, Inc., San Diego, California 92121, United States

Pacific Sleep Medicine Services, Inc., Los Angeles, California 90048, United States

Pacific Sleep Medicine Services, Inc., El Centro, California 92243, United States

Memory Disorder Center, Pompano Beach, Florida 33064, United States

Seth Hochman, MD, Miami, Florida 33156, United States

Liliana Montoya, MD, Port Charlotte, Florida 33952, United States

Roskamp Institute Memory Clinic, Tampa, Florida 33617, United States

Collier Neurologic Specialists, Naples, Florida 34102, United States

Palm Beach Neurology, West Palm Beach, Florida 33407, United States

Segal Institute for Clinical Research, North Miami, Florida 33161, United States

MD Clinical, Hallandale Beach, Florida 33009, United States

Berma Research Group, Hialeah, Florida 33016, United States

Cleveland Clinic Florida, Weston, Florida 33331, United States

Cuervo Research Group, Miami, Florida 33143, United States

Bradenton Research Center, Bradenton, Florida 34205, United States

Parkinson's Disease Movement Disorders Center - Boca Raton, Boca Raton, Florida 33486, United States

Ocala Neurodiagnostic Center, Ocala, Florida 34471, United States

Eastern Research, Hialeah, Florida 33013, United States

Lozano, Cosme, MD, Joliet, Illinois 60435, United States

The Northwestern Alzheimer's Center, Chicago, Illinois 60611, United States

Rush Alzheimer's Disease Center, Chicago, Illinois 60612, United States

University of Nevada School of Medicine,, Las Vegas, Nevada 89102, United States

ClinSearch Inc., Kenilworth, New Jersey 07033, United States

University of New Mexico School of Medicine, Department of Psychiatry, Albuquerque, New Mexico 87131, United States

New York University School of Medicine, Aging and Dementia Research Center, New York, New York 10016, United States

The Burke Rehabilitation Hospital, White Plains, New York 10605, United States

North Carolina Neuropsychiatry, PA, Charlotte, North Carolina 28209, United States

Clinical Research Associates, Inc., Oklahoma City, Oklahoma 73118, United States

The Penn Ralston Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

Clinical Research Center, Jenkintown, Pennsylvania 19046, United States

University of Texas Mental Sciences Insitute, Houston, Texas 77030, United States

University of Texas, Health Science Center-San Antonio, San Antonio, Texas 78229, United States

Christopher Ticknor, MD, San Antonio, Texas 78229, United States

Starting date: December 2005
Ending date: December 2007
Last updated: February 29, 2008