Source: Cancer Immunity  |  Posted 9 years ago

DENVER, CO -- April 17, 2002 -- New data demonstrates that treatment with Aricept? (donepezil hydrochloride) significantly improved cognition and confirmed benefits on global (overall) function, compared with placebo, in patients with vascular dementia (VaD).
The data, presented today at the American Academy of Neurology (AAN) annual meeting, reinforces findings from an earlier study that demonstrated Aricept was both effective and well tolerated in patients with VaD. Both studies followed strict criteria to enroll only patients with VaD and no prior diagnosis of Alzheimer's disease (AD).
Aricept is currently indicated for the treatment of mild to moderate AD.
"In these groundbreaking studies -- the largest clinical trials to study VaD -- Aricept has been shown to improve cognitive function in patients with VaD. These results are extremely important because currently there are no approved treatments for this condition," said Raymond Pratt, MD, senior director, Clinical Research, Eisai Inc. "It is important for VaD patients and their caregivers to know that cognitive decline caused by stroke -- including confusion, memory loss, impaired orientation, and impaired judgment -- is a condition in and of itself which may benefit from treatment."
This study of 603 patients is the second of two trials examining the efficacy and safety of Aricept in patients with VaD. The first study, presented in the U.S. earlier this year at the American Association for Geriatric Psychiatry's 15th annual meeting, included 616 patients and also reported significant improvements in cognition and function with treatment of Aricept in patients with VaD. Eisai Co., Ltd., 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.
"Although there is an overall awareness and understanding about the physical side effects associated with stroke, few realize the serious impact a stroke can have on cognition by causing dementia," said Phil Gorelick, M.D, director of the Center for Stroke Research at Rush Neuroscience Institute in Chicago. "This research offers hope to patients affected by VaD, because we see how a therapy can help manage the cognitive decline associated with cerebrovascular disease."
VaD is characterized by cognitive decline most often caused by a single, localised or series of strokes. In contrast to untreated patients with AD, who often experience a gradual, progressive decline, untreated patients with VaD typically experience a stepwise cognitive decline. Common cognitive symptoms of VaD include impairment of orientation, attention, language skills, calculations, motor control, functionality, abstraction and judgment. VaD is directly correlated with risk factors for stroke, including high blood pressure, diabetes, elevated cholesterol levels and smoking.
VaD is the second most common form of dementia, accounting for up to one-third of all diagnosed dementia cases in the United States. The prevalence of VaD increases with age and, as the number of people in the U.S. age 65 and older is expected to grow to 69.4 million by the year 2030, VaD can be expected to be a growing healthcare issue among the elderly population.
This 24-week, double-blind, randomised, placebo-controlled study included 603 men and women with VaD and no prior diagnosis of AD. Patients were selected using research criteria specifically designed to identify patients with VaD developed by the National Institute of Neurological Disorders and Stroke (NINDS) with support from the Association International 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 skills, visuospatial functions, executive functions, motor control, and praxis.
The majority of participants in this study had a history of stroke. Virtually all participants (99.2 percent) took one or more other medications, most frequently to treat cardiovascular risk factors, with over 80 percent receiving some form of medication to prevent strokes.
Participants received daily doses of either 5 mg Aricept, 10 mg Aricept, or placebo. Patients in the study were evaluated using five separate measures of assessment; The Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC-plus), the Alzheimer's Disease Functional Assessment and Change Scale (ADFACS) and the Clinical Dementia Rating-sum of the boxes (CDR-SB). These analyses are based on observed cases of patients who had a final evaluation at week 24.
Patients showed significant improvement in their cognitive function compared to those taking placebo (p = 0.002 for the 5 mg dose; p <0.001 for the 10 mg dose), as measured by the Alzheimer's Disease Assessment Scale (ADAS-cog).
Patients showed improvement in cognitive function, compared to the baseline score, measured by the Mini-Mental State Examination (MMSE), for both dosages. Using this measurement, a significant improvement was observed in patients treated with the 10 mg dose, compared to placebo (p = .16 for the 5 mg dose; p <0.01 for the 10 mg dose).
In contrast to AD patients treated with placebo, patients in this study who received placebo showed no change in cognitive function as measured by ADAS-cog and MMSE.
Significant improvements in global function were observed in patients at the 5 mg Aricept dose, compared to patients who received placebo (p = 0.01 for the 5 mg dose), as measured by the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC-plus). Improvement for patients on the 10 mg dose was not significantly better than placebo (p = 0.27, 10 mg).
Functional deterioration was significantly slowed in patients treated with both doses of Aricept compared with placebo (p=.02 for the 5 mg dose; p=.04 for the 10 mg dose), as measured by the Alzheimer's Disease Functional Assessment and Change Scale (ADFACS).
At week 24, statistically significant improvement in global function was observed in patients receiving Aricept 10 mg (p=.01) but not 5 mg (p=.35) as measured by the Clinical Dementia Rating-sum of the boxes (CDR-SB).
"Typically, VaD patients are being treated concomitantly for several other serious cardiovascular diseases, such as high blood pressure, high cholesterol and diabetes," said Dr. Gorelick. "Physicians treating patients with VaD need to be confident that any new medicine they prescribe is tolerable and will not interact with medications patients are already taking. The fact that over 80 percent of this sick and heavily-medicated patient population completed the treatment regimen is very encouraging and shows that with Aricept, patients may be able to manage VaD symptoms and their overall health at the same time."
Overall, adverse events did not differ substantially in frequency between the Aricept groups (88.9 percent for 5 mg patients; 94.7 percent for 10 mg patients) and the placebo group (88.4 percent). Rates of cardiovascular events were also similar among all study participants (20.7 percent for 5 mg group; 20.4 percent for 10 mg group; 18.1 percent for placebo). As expected, and consistent with the drug's known mechanism of action, digestive system side effects reported, including diarrhea, nausea and vomiting, occurred more frequently in Aricept-treated patients than placebo-treated patients.
Other adverse events that occurred significantly more often in Aricept-treated patients included headache, anorexia, cramps, and abnormal dreams. Overall, 478 patients (79.3 percent) completed the study and 125 (20.7 percent) discontinued, including 89 (14.8 percent) who discontinued due to an adverse event. No deaths were considered to be related to Aricept.
SOURCE: Eisai Inc.; Pfizer Inc