ARICEPT® efficacy and safety study in new treatment area presented at the Second International Congress on Vascular Dementia
Salzburg, Austria - Treatment with ARICEPT® (donepezil hydrochloride tablets) significantly improved the cognitive and global (overall) function of patients with vascular dementia (VaD), compared with placebo, according to results from a first-of-its-kind clinical study presented today at the Second International Congress on Vascular Dementia (ICVD) in Salzburg, Austria. Only patients with VaD were included in this study. Patients with a diagnosis of Alzheimer’s disease (AD) were excluded. ARICEPT® is currently indicated for the treatment of mild to moderate AD.
VaD, cognitive decline caused by a single, localized stroke, or series of strokes, is second only to AD as a cause of dementia. Up to one-third of all diagnosed dementia cases are VaD. In Europe, the prevalence of VaD is estimated to be 1.5 to 4.8 percent for people 70 to 80 years of age; of the patients over 65 years old diagnosed with dementia in the United States, approximately 9 to 39 percent have VaD.
This study is one of two conducted to examine the efficacy and safety of ARICEPT® in patients with VaD, excluding patients diagnosed with AD. The results of the second study are expected to be released in mid 2002. Eisai, which discovered and developed ARICEPT®, will work with its strategic alliance partner, Pfizer Inc., to file both studies with regulatory authorities worldwide for an indication to treat VaD.
"This groundbreaking study is the first time a cholinesterase inhibitor has been studied in a population composed primarily of patients with vascular dementia. VaD is a condition that has been underdiagnosed and undertreated," said Raymond D. Pratt, M.D., senior director, clinical research, Eisai Inc., who presented the data at the Second International Congress on Vascular Dementia. “These results suggest ARICEPT® may be a promising option in treating VaD – a condition for which there is currently no approved treatment.”*
VaD is directly correlated with risk factors for stroke, including high blood pressure, diabetes, elevated cholesterol levels and smoking. The prevalence of VaD increases with age. Patients with VaD typically experience a stepwise decline in function, in contrast to patients with AD, who often experience a gradual, progressive decline. Like all forms of dementia, VaD results in significant physical, financial and emotional burden for patients and their families.
Study details
The study included patients with VaD and excluded those with a diagnosis of AD. Patients were selected using research criteria specifically designed to identify patients with VaD. The criteria were developed by the National Institute of Neurological Disorders and Stroke (NINDS) with support from the Associate Internationale pour la Recherche et l'Enseignment en Neurosciences (AIREN).
The NINDS-AIREN criteria define VaD as cognitive decline involving memory loss, as well as impairment in at least two other cognitive domains that interfere with activities of daily life. These domains include orientation, attention, language-verbal skills, coordination, calculations, executive functions, motor control, functionality, abstraction, and judgment. Patients were also required to have neuroimaging evidence of cerebrovascular disease obtained by a computed tomography (CT) scan or magnetic resonance imaging (MRI).
This 24-week, double-blind, randomized, placebo-controlled study, included 616 men and women with VaD, with an average age of 75 years. The majority of participants had a history of stroke. Virtually all (99.7 percent) participants took one or more other medications, most frequently to prevent cardiovascular risk factors, with over 80 percent receiving some form of medication to prevent strokes.
Participants received daily doses of either 5 milligrams (mg) ARICEPT® (donepezil hydrochloride tablets), 10 mg ARICEPT® or placebo. Patients who received ARICEPT® showed significant improvement in their cognitive function compared to those taking placebo (P = 0.001, 5 mg; P <0.0001, 10 mg), as measured by the Alzheimer's Disease Assessment Scale (ADAS-cog), a standard test of cognitive abilities. Evaluation of global function also revealed significant improvements for patients at both ARICEPT® doses compared to patients who received placebo (P= 0.004 and P= 0.047, respectively), as measured by the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC-plus), a standard global assessment tool.
"Patients with VaD are often prescribed numerous medications to treat primary cardiovascular diseases such as blood pressure, cholesterol-lowering and diabetes drugs," said Sandra E. Black, M.D., Head, Division of Neurology, Sunnybrook & Women's College Health Sciences Centre, University of Toronto. "In this study, ARICEPT® was well-tolerated, even when taken with other medications."
Adverse events
Overall, adverse events did not differ significantly in frequency between the ARICEPT® (donepezil hydrochloride tablets) groups (90.4 percent for 5 mg patients; 91.6 percent for 10 mg patients) and the placebo group (86.5 percent). Rates of cardiovascular events were also similar among all study participants (19 percent for 5 mg group; 20 percent for 10 mg group; 22 percent for placebo). As expected and consistent with the drug's known mechanism of action, side effects related to the digestive system, including diarrhea and nausea, occurred more frequently in ARICEPT® -treated patients than placebo-treated patients. Other adverse events that occurred significantly more often in ARICEPT(R)-treated patients were accidental injury, insomnia, leg cramps, rhinitis, and abnormal dreams. Overall, 491 patients (79.7 percent) completed the study and 125 (20.3 percent) discontinued, including 73 (11.9 percent) who discontinued due to an adverse event. No deaths were considered to be related to ARICEPT®.
Information about ARICEPT® treatment in Alzheimer’s disease
Once-a-day prescription ARICEPT®, indicated for mild to moderate Alzheimer's disease, can improve cognition and maintain patient function. In a progressively degenerative disease such as Alzheimer's, improvement, stabilization or a less-than-expected decline over time is considered a positive response to treatment. These types of responses have been observed in patients treated with ARICEPT® in clinical trials. Individual responses to treatment may vary.
ARICEPT® (donepezil hydrochloride tablets) is well tolerated but may not be for everyone. Some people may experience nausea, diarrhea, insomnia, vomiting, muscle cramps, fatigue or loss of appetite. In studies, these effects were usually mild and temporary. Some people taking ARICEPT® may experience fainting. People at risk for ulcers should tell their doctors because their condition may get worse.
ARICEPT® is available by prescription in more than 50 countries. In November 1994, Eisai Co., Ltd. and Pfizer Inc announced the formation of a strategic alliance for the promotion of ARICEPT® and development of new treatments for Alzheimer's disease and other cognitive disorders. First launched in the United States in February 1997, ARICEPT® has been well-received in the Alzheimer's disease community with more than 717 million days of patient use worldwide, and more than 1.6 million people in the United States have received a prescription for ARICEPT®. Eisai Co., Ltd., and Pfizer Inc are committed to a collaboration dedicated to advances in Alzheimer's therapy. These studies were funded by Eisai.
Full prescribing information is available upon request from Melissa Furrie of Porter Novelli.
Additional contact information:
Susan Yarin
Pfizer Inc.
212-733-5260
ARICEPT® is a registered trademark of Eisai Co., Ltd.
News Source: Eisai Ltd. (European Office) and Pfizer Inc.
[DON #141.01A] @ Pfizer Inc & Eisai Co. Ltd. All rights reserved.
Contact:
Melissa Furrie, 212-601-8232
Stephanie Scott, 212-601-8146