TOKYO, Japan, March 16 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, President and CEO: Haruo Naito) today announced preliminary results from the latest donepezil (Product name: ARICEPT(R)) study (Study 319) on the treatment of people with vascular dementia (VaD). Preliminary efficacy results show that those who received donepezil improved on measures of cognition, but not global function (overall clinical effect), compared with those who received placebo. While there was no statistically significant difference in the overall occurrence of adverse events, there were more deaths observed in the donepezil group than in the placebo group. Consistent with Eisai's standard practice, these safety results were reported to regulatory authorities and investigators currently participating in donepezil clinical trials. In the US, Japan, and in the EU, donepezil is approved only for the treatment of mild to moderate Alzheimer's Disease (AD) and not for VaD. In India, New Zealand, the Philippines, Romania, South Korea and Thailand it is also approved for the treatment of VaD.
This VaD trial was a multi-center, randomized, double blind study conducted in nine countries. The study was designed to enroll only people with VaD and with no prior diagnosis of AD. Patients were randomized to 5 mg of donepezil or placebo in a 2:1 ratio. Donepezil was administered once daily for 24 weeks. As in two previous VaD studies with donepezil, the majority of participants in this trial had a history of stroke and/or heart disease and most were taking other medications, most frequently to treat cardiovascular risk factors.
In this latest study, participants treated with donepezil showed statistically significant improvement on the primary measure of cognitive function (V-ADAS-cog)(1) as compared to those who received placebo. No statistically significant benefit was observed on the other primary measure, the CIBIC-plus(2), which evaluates global function. Some of the secondary measures for cognitive function showed statistically significant benefit, while others did not. These results are generally consistent with the two previously published studies of donepezil in VaD.
A review of the safety data for this most recent study found a difference in the percent of study participants who died in the donepezil group and the placebo group. There were 11 deaths reported in the donepezil group of 648 study participants and none in the group of 326 people given placebo.
An analysis showed the following:
-- The mortality rate for the donepezil treatment group in Study 319 (1.7%) was consistent with that observed for the donepezil treated group (1.7%) in a combined analysis of the two previous VaD studies (Studies 307 and 308) and is lower than that reported in the general VaD population.
-- The death rate observed in the placebo group in Study 319 (0.0%) is lower than that seen in the placebo groups (2.0%) in the combined analysis for the two prior VaD studies (Studies 307 and 308) and that reported in the general VaD population. This unexpectedly low mortality rate is an unusual finding in this population, considering the age and pathology in patients in the study.
-- An analysis of all three VaD trials (Studies 307, 308 and 319) shows no statistically significant difference in observed mortality rates between the donepezil and placebo groups (1.7% vs. 1.1%).
-- Because VaD patients are at risk for vascular events such as stroke and myocardial infarction, additional analyses of these events were performed for the three VaD studies alone and in combination. None of these analyses showed a statistically significant higher risk of a vascular event in the donepezil group compared to placebo.
Overall adverse events in this most recent study did not differ significantly in frequency between those participants receiving donepezil and those receiving placebo. Consistent with donepezil's known mechanism of action, adverse events that occurred at a rate of greater than 5% and twice the rate of placebo were abdominal pain (5.1% vs. 2.5%), anorexia (5.7% vs. 2.8%) and nausea (9.9% vs. 4.3%).
Eisai will continue to engage in discussions with regulatory authorities regarding the donepezil VaD program.
Eisai has reported to regulatory authorities worldwide that it is the company's position that the results of this VaD study do not change the overall safety profile of donepezil and that its benefit-risk profile continues to be favorable for its approved indications.
(1)V-ADAS-cog: Vascular-Alzheimer's Disease Assessment Scale - cognitive subscale
(2)CIBIC-plus - Clinician's Interview-Based Impression of Change with caregiver input
About Eisai Co., Ltd.
Eisai Co., Ltd. is a research-based human health care (hhc) company that discovers, develops and markets products in more than 30 countries. Eisai focuses its efforts in three therapeutic areas: neurology, gastro-intestinal disorders and oncology/critical care. Through a global network of research facilities, manufacturing sites and marketing subsidiaries, Eisai actively participates in all aspects of the worldwide health care system. Eisai employs more than 8,000 people worldwide and forecasts the group sales of GBP2.9billion (EUR4.18billion) in FY2005. Currently, more than 50% of the group sales is derived from overseas business. For more information on Eisai Co., Ltd, please visit
www.eisai.co.jp
Media enquiries: In Europe please contact the Eisai Corporate Communications Department on Office: +44-(0)-20-8600-1400, Mobile: +44-(0)-7973-411-419
